Bio

Bio

Ruth Lathi, MD graduated Massachusetts Institute of Technology with a B.S. in Molecular Biology; she earned her M.D. degree at University of California, San Francisco, and completed her residency training in obstetrics and gynecology at Baylor College of Medicine. She completed her sub-specialty fellowship training in reproductive endocrinology and infertility (REI) at Stanford University.

Dr. Lathi joined the faculty at Stanford University in 2003 and is currently a Professor in the Department of Obstetrics and Gynecology, Director of the Multi-specialty Recurrent Pregnancy Loss program at Stanford, and is the Program Director of the REI Fellowship. Dr. Lathi has a special interest in treating recurrent pregnancy loss, the role of preimplantation genetic diagnosis in the treatment of reproductive disorders, and the prognostic value and utility of genetic testing of miscarriage tissues, and long-term outcomes of fertility treatments.

Dr. Lathi enjoys mentoring medical students, residents and fellows, and spending time with her family and outdoor activities like golfing, swimming and hiking.

Clinical Focus

  • Fertility (Reproductive Medicine)
  • Recurrent Pregnancy Loss and Miscarriage
  • Gynecology
  • Preimplantation Genetic Diagnosis
  • Obstetrics and Gynecology

Academic Appointments

Administrative Appointments

  • Fellowship Director, Stanford, Reproductive Endocrinology and Infertility (2019 - Present)
  • Director, Clinical Operations, Stanford Fertility and Reproductive Health (2015 - 2019)
  • Associate Director of the REI fellowship, Stanford University (2004 - 2015)
  • President, Pacific Coast Reproductive Society (2015 - 2016)
  • Director, Recurrent Pregnancy Loss Program, Reproductive Endocrinology & Infertilty Division, Stanford University (2007 - Present)

Honors & Awards

  • CREOG - Faculty Teaching Award, Stanford University Medical Center, Department of Obstetrics and Gynecology (2006)

Boards, Advisory Committees, Professional Organizations

  • Member, Editorial Board of Sexuality, Reproduction and Menopause Journal (2007 - 2013)
  • Member, Board of Directors for Pacific Coast Reproductive Society (2010 - 2015)
  • Member, Strategic Planning Committee for Pacific Coast Reproductive Society (2011 - 2016)
  • Founding Member, Early Pregnancy Special Interest Group, American Society for Reproductive Medicine (2011 - Present)

Professional Education

  • Fellowship, Stanford University, Reproductive Endocrinology & Infertility (2003)
  • Residency: Baylor College of Medicine Registrar (2000) TX
  • Internship: Baylor College of Medicine Registrar (1997) TX
  • Medical Education: Univ of California San Francisco (1996) CA
  • Board Certified, American Board of OB/GYN, Reproductive Endocrinology and Infertility (2006)
  • Board Certified, American Board of OB/GYN, Obstetrics and Gynecology (2005)
  • MD, UC-San Francisco, Medicine (1996)
  • BS, M.I.T., Biology (1992)

Contact

  • Tracy Lindsay Administrative Assistant
    • Tel: 650.498.7408
  • Stanford Medicine Fertility and Reproductive Health 1195 W Fremont Ave Sunnyvale, CA 94087
    • Tel: (650) 498-7911
    Fax: (669) 233-2888

Links

Research & Scholarship

Current Research and Scholarly Interests

Dr. Lathi?s longstanding interest in miscarriage and recurrent pregnancy loss has led to multiple completed studies on the contribution of embryonic chromosome errors on miscarriage and recurrent miscarriage patients. She has published extensively, on ways to optimize testing of miscarriage and the impact of environmental factors such as age, obesity and endocrine disrupting chemicals on the chromosome make up of miscarriages. Her current research in the field for recurrent pregnancy loss focusses on endometrial contributions to miscarriage, such as progesterone resistance and inflammation, as well as, the contribution of sperm quality to miscarriage.

The use of preimplantation genetic testing in the setting of infertility and recurrent miscarriage is controversial, her research explores the risks, benefits, costs and limitations of this treatment. Embryo mosaicism (the combination of normal and abnormal cells within an embryo) leads to inaccuracies in preimplantation genetic testing. Dr. Lathi is currently performing an observational trial to better understand the implantation potential of mosaic embryos.

Dr. Lathi recently received NIH funding to study pregnancy outcomes after frozen embryo transfers. Some studies have linked frozen embryo transfer to pre-eclampsia, fetal macrosomia and other placental disorders. Dr. Lathi will be recruiting for a multi-site trial to observe differences in maternal and fetal outcomes based on which fertility medications were used prior to implantation and in the first trimester.

Clinical Trials

  • Pregnancy and Developmental Outcomes After Transfer of Reportedly Aneuploid or Mosaic Embryos Recruiting

    To determine how often embryos reported to be abnormal by preimplantation genetic testing result in liveborn infants. To evaluate whether the pregnancies that result from these embryos are higher risk for complications and whether the resulting babies have higher risk for health or developmental issues in the first five years after birth.

    View full details

  • Predicting Endometrial Receptivity for Optimal Reproductive Management Not Recruiting

    The purpose of this study is to understand why some women are infertile (unable to conceive a child). The investigators hope to learn if an endometrial biopsy after egg retrieval is feasible for detecting biomarkers for endometriosis and predicting implantation and pregnancy rate after embryo transfer. This study design will provide for the first time, an opportunity to compare endometrial biopsy material from hyperstimulated (gonadotropin treated) subjects after egg retrieval. If successful, it would provide a new protocol for women with unexplained infertility or those with known endometriosis to avoid poor IVF outcomes.

    Stanford is currently not accepting patients for this trial. For more information, please contact Study team, 408-688-9892.

    View full details

  • Preimplantation Genetic Testing in Women of Advanced Maternal Age Not Recruiting

    The GETSET trial is a prospective randomized trial designed to evaluate the clinical outcomes of incorporating preimplantation genetic testing for aneuploidies (PGT-A) in elective single embryo transfer in women between 35 and 40 years of age.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ruth B Lathi, MD, (650) 498 - 7911.

    View full details

Teaching

2020-21 Courses

Publications

All Publications

  • Does an increased body mass index affect endometrial gene expression patterns in infertile patients? A functional genomics analysis. Fertility and sterility Comstock, I. A., Diaz-Gimeno, P., Cabanillas, S., Bellver, J., Sebastian-Leon, P., Shah, M., Schutt, A., Valdes, C. T., Ruiz-Alonso, M., Valbuena, D., Simon, C., Lathi, R. B. 2017; 107 (3): 740-748 e2

    Abstract

    To analyze the transcriptomic profile of endometrial gene alterations during the window of implantation in infertile obese patients.Multicenter, prospective, case-control study.Three academic medical centers for reproductive medicine.Infertile patients, stratified into body mass index (BMI) categories according to the World Health Organization guidelines, were included in the study.Endometrial samples were obtained from women undergoing standardized estrogen and P replacement cycles after 5 days of vaginal P supplementation.To identify endometrial gene expression alterations that occur during the window of implantation in infertile obese patients as compared with infertile normal-weight controls using a microarray analysis.XCL1, XCL2, HMHA1, S100A1, KLRC1, COTL1, COL16A1, KRT7, and MFAP5 are significantly dysregulated during the window of implantation in the receptive endometrium of obese patients. COL16A1, COTL1, HMHA1, KRCL1, XCL1, and XCL2 were down-regulated and KRT7, MFAP5, and S100A1 were up-regulated in the endometrium of obese patients. These genes are mainly involved in chemokine, cytokine, and immune system activity and in the structural extracellular matrix and protein-binding molecular functions.Obesity is associated with significant endometrial transcriptomic differences as compared with non-obese subjects. Altered endometrial gene expression in obese patients may contribute to the lower implantation rates and increased miscarriage rates seen in obese infertile patients.NCT02205866.

    View details for DOI 10.1016/j.fertnstert.2016.11.009

    View details for PubMedID 27919438

  • A RETROSPECTIVE STUDY EXAMINING PHENTERMINE ON PRECONCEPTION WEIGHT LOSS AND PREGNANCY OUTCOMES. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists Chang, J. J., Lathi, R. B., Kim, S. H. 2020

    Abstract

    Background: Obesity is a well-known risk factor for infertility. However, use of weight loss medications prior to conception is underutilized. The objectives of our study are to describe weight loss, pregnancy rates, and live birth rates after short-term phentermine use in women with obesity and infertility. Methods: This was a retrospective analysis of 55 women (18-45 years old) who were overweight or obese, diagnosed with infertility, and prescribed phentermine for weight loss in an ambulatory endocrinology clinic at a single, tertiary level academic medical center. Main outcome measures were mean percent weight change at 3 months after starting phentermine and pregnancy and live birth rates from start of phentermine to June 30, 2017. Results: Median duration of phentermine use was 70 days (Q1, Q3 [33, 129]). Mean ± SD percent weight change at 3 months after starting phentermine was -5.3 ± 4.1% (p < 0.001). The pregnancy rate was 60% and live birth rate was 49%. There was no significant difference in pregnancy rates (52% vs. 68%, p = 0.23) or live birth rates (44% vs. 54%, p = 0.50) in women who lost ?5% vs. <5% of their baseline weight. Number of metabolic comorbidities was negatively associated with pregnancy rate. Phentermine was generally well tolerated with no serious adverse events. Conclusions: Phentermine can produce clinically significant weight loss in women with obesity during the preconception period. Higher pregnancy or live birth rates were not observed with greater degree of weight loss with phentermine.

    View details for DOI 10.4158/EP-2019-0609

    View details for PubMedID 32407664

  • Preimplantation genetic testing for aneuploidy in poor ovarian responders with four or fewer oocytes retrieved. Journal of assisted reproduction and genetics Deng, J., Hong, H. Y., Zhao, Q., Nadgauda, A., Ashrafian, S., Behr, B., Lathi, R. B. 2020

    Abstract

    PURPOSE: To assess whether preimplantation genetic testing for aneuploidies (PGT-A) at the blastocyst stage improves clinical outcomes compared with transfer of embryos without PGT-A in poor ovarian response (POR) patients.METHODS: Retrospective cohort study of IVF cycles from 2016 to 2019 at a single academic fertility center. IVF cycles with POR and four or fewer oocytes retrieved were stratified into PGT-A (n=241) and non-PGT (n=112) groups. In PGT-A cycles, trophectoderm biopsy, next-generation sequencing with 24-chromosome screening, and single euploid frozen embryo transfer were performed. In non-PGT cycles, fresh or frozen transfer of untested embryos on day 3 or 5 was performed. Main outcomes included live birth rate and miscarriage rate per retrieval.RESULT(S): Patients who underwent PGT-A cycles were significantly less likely to reach embryo transfer compared with those who underwent non-PGT cycles (13.7% vs 70.6%). The live birth rate per retrieval did not differ between the PGT-A and non-PGT groups (6.6% vs 5.4%). Overall, the miscarriage rate was low. The PGT-A group demonstrated a significantly lower miscarriage rate per retrieval (0.4% vs 3.6%) as well as per pregnancy (5.9% vs 40.0%) compared with the non-PGT group. The number needed to treat to avoid one clinical miscarriage was 31 PGT-A cycles.CONCLUSION(S): PGT-A did not improve live birth rate per retrieval in POR patients with four or fewer oocytes retrieved. PGT-A was associated with a lower miscarriage rate; however, a fairly large number of PGT-A cycles were needed to prevent one miscarriage.

    View details for DOI 10.1007/s10815-020-01765-y

    View details for PubMedID 32285297

  • The impact of culture conditions on blastocyst formation and aneuploidy rates: a comparison between single-step and sequential media in a large academic practice. Journal of assisted reproduction and genetics Deng, J., Zhao, Q., Cinnioglu, C., Kayali, R., Lathi, R. B., Behr, B. 2020

    Abstract

    PURPOSE: To compare a single-step medium with a sequential medium on human blastocyst development rates, aneuploidy rates, and clinical outcomes.METHODS: Retrospective cohort study of IVF cycles that used Sage advantage sequential medium (n = 347) and uninterrupted Sage 1-step medium (n = 519) from July 1, 2016, to December 31, 2017, in an academic fertility center. Main outcome measures are blastocyst formation rates per two-pronuclear (2PN) oocyte and aneuploidy rates per biopsy.RESULTS: Of all IVF cycles, single-step medium yielded higher blastocyst formation rate (51.7% vs 43.4%) but higher aneuploidy rate (54.0% vs 45.8%) compared with sequential medium. When stratified by maternal age, women under age 38 had no difference in blastocyst formation (52.2% vs 50.2%) but a higher aneuploidy rate (44.5% vs 36.4%) resulting in a lower number of euploid blastocysts per cycle (2.6 vs 3.3) when using single-step medium compared to sequential medium. In cycles used single-step medium, patients ? age 38 had higher blastocyst rate (48.0% vs 33.6%), but no difference in aneuploidy rate (68.8% vs 66.0%) or number of euploid embryos (0.8 vs 1.1). For patients reaching euploid embryo transfer, there was no difference in clinical pregnancy rates, miscarriage rates, or live birth rates between two culture media systems.CONCLUSIONS: Our study demonstrates an increase in aneuploidy in young women whose embryos were cultured in a single-step medium compared to sequential medium. This study highlights the importance of culture conditions on embryo ploidy and the need to stratify by patient age when examining the impact of culture conditions on overall cycle potential.

    View details for DOI 10.1007/s10815-019-01621-8

    View details for PubMedID 31950455

  • INCREASED RISK OF SEVERE MATERNAL MORBIDITY AMONG INFERTILE WOMEN: ANALYSIS OF US CLAIMS DATA. American journal of obstetrics and gynecology Murugappan, G., Li, S., Lathi, R. B., Baker, V. L., Luke, B., Eisenberg, M. L. 2020

    Abstract

    Severe maternal morbidity continues to be an issue of national and global concern and is increasing in incidence. The incidence of infertility is also on the rise, and infertile women experience a higher risk of incident chronic medical disease and cancer, suggesting that fertility may serve as a window to a woman's overall health.To investigate the risk of severe maternal morbidity by maternal fertility status.Retrospective cohort analysis using Optum's de-identifed Clinformatics® Data Mart Database between 2003-2015. Infertile women stratified by infertility diagnosis, testing or treatment were compared to fertile women seeking routine gynecologic care. In both groups, only women who underwent pregnancy and delivery of a singleton during the follow up period were included. Main outcomes were severe maternal morbidity indicators, defined by the CDC, and identified by ICD-10 and CPT codes within 6 weeks of each delivery. Results were adjusted for maternal age, race, education, nulliparity, race, smoking, obesity, delivery mode, preterm birth, number of prenatal visits, and year of delivery.19,658 women comprised the infertile group and 525,695 women comprised the fertile group. The overall incidence of any severe maternal morbidity indicator was 7.0% among women receiving fertility treatment, 6.4% among women receiving a fertility diagnosis, 5.5% among women receiving fertility testing and 4.3% among fertile women.. Overall, infertile women had a significantly higher risk of developing any severe maternal morbidity indicator (AOR 1.22, CI 1.14-1.31, p<0.01) as well as a significantly higher risk of disseminated intravascular coagulation (DIC) (AOR 1.48, CI 1.26 - 1.73, p<0.01), eclampsia (AOR 1.37, CI 1.05 - 1.79, p<0.01), heart failure during procedure or surgery (AOR 1.54, CI 1.21 - 1.97, p<0.01), internal injuries of the thorax, abdomen or pelvis (AOR 1.59, CI 1.12 - 2.26, p<0.01), intracranial injuries (AOR 1.77, CI 1.20- 2.61, p<0.01), pulmonary edema (AOR 2.18, CI 1.54 - 3.10, p<0.01), thrombotic embolism (AOR 1.58, CI 1.14 - 2.17, p<0.01), and blood transfusion (AOR 1.50, CI 1.30 - 1.72, p<0.01) compared to fertile women. Fertile women did not face a significantly higher risk of any maternal morbidity indicator compared to infertile women. In subgroup analysis by maternal race/ethnicity, the likelihood of severe morbidity was significantly higher among fertile Black women compared to fertile Caucasian women. There was no difference between infertile Black and Caucasian women after multivariable adjustment.Using an insurance claims database, we report that women diagnosed with infertility and women receiving fertility treatment experience a significantly higher risk of multiple indicators of severe maternal morbidity compared to fertile women. The increased risk of severe maternal morbidity noted among fertile Black women compared to fertile Caucasian women is attenuated among infertile Black women, who face similar risks as infertile Caucasian women.

    View details for DOI 10.1016/j.ajog.2020.02.027

    View details for PubMedID 32112734

  • Levonorgestrel IUD: is there a long-lasting effect on return to fertility? Journal of assisted reproduction and genetics Dinehart, E., Lathi, R. B., Aghajanova, L. 2019

    Abstract

    Intrauterine devices (IUDs) are effective and safe long-acting reversible contraceptive methods for preventing unplanned pregnancies. While extensive studies were conducted to evaluate return to fertility after removal of IUDs, majority of them were focused on multiparous women using copper IUDs. Current trends indicate increased use of levonorgestrel (LNG) IUDs in nulliparous women for very long periods of time, with both nulliparity and long duration of LNG-IUD use being potentially associated with trends towards longer time to conception post removal. Understanding the effects that LNG-IUDs may have on endometrial morphology and gene expression has important implications to further understanding their mechanism of action. Studies examining endometrial gene expression show persistent changes in receptivity markers up to 1 year after removal of an inert IUD, and no similar studies have been performed after removal of LNG-IUDs. Given the current gap in the literature and trends in LNG-IUD use in nulliparous young women, studies are needed that specifically look at the interaction of nulliparity, long-term use of LNG-IUD, and return to normal fertility. Herein, we review the available literature on the mechanism of action of IUDs with a specific focus on the effect on endometrial gene expression profile changes associated with IUDs.

    View details for DOI 10.1007/s10815-019-01624-5

    View details for PubMedID 31709489

  • THE IMPACT OF SPONTANEOUS LH SURGE DURING A NATURAL CYCLE FROZEN EMBRYO TRANSFER. Johal, J. K., Bavan, B., Lathi, R. B., Milki, A. A. ELSEVIER SCIENCE INC. 2019: E171

    View details for DOI 10.1016/j.fertnstert.2019.07.564

    View details for Web of Science ID 000487821301184

  • PREIMPLANTATION GENETIC TESTING FOR ANEUPLOIDY (PGT-A) REDUCES MISCARRIAGE AND IMPROVES LIVE BIRTH RATES IN RECURRENT PREGNANCY LOSS PATIENTS. Kim, J. G., Murugappan, G., Lathi, R. B., Kort, J. D., Hanson, B. M., Tiegs, A. W., Osman, E. K., Neal, S. A., Scott, R. ELSEVIER SCIENCE INC. 2019: E401

    View details for DOI 10.1016/j.fertnstert.2019.07.1141

    View details for Web of Science ID 000487821304003

  • IS ANTIMULLERIAN HORMONE PREDICTIVE OF OUTCOMES AFTER PGT-A IN PATIENTS WITH RECURRENT PREGNANCY LOSS? Murugappan, G., Shahine, L. K., Lathi, R. B. ELSEVIER SCIENCE INC. 2019: E403

    View details for DOI 10.1016/j.fertnstert.2019.07.1145

    View details for Web of Science ID 000487821304007

  • THE IMPACT OF PATERNAL AGE ON REPRODUCTIVE OUTCOMES IN THE SETTING OF A EUPLOID SINGLE EMBRYO TRANSFER ACHIEVED WITH SURGICALLY EXTRACTED SPERM. Hanson, B. M., Kim, J. G., Tiegs, A. W., Osman, E. K., Neal, S. A., Lathi, R. B., Scott, R., Franasiak, J. M. ELSEVIER SCIENCE INC. 2019: E108

    View details for DOI 10.1016/j.fertnstert.2019.07.1343

    View details for Web of Science ID 000487821301026

  • BLASTOCYST GRADE PREDICTS OUTCOME AFTER FROZEN EUPLOID TRANSFER IN PATIENTS WITH RECURRENT PREGNANCY LOSS. Murugappan, G., Kim, J. G., Kort, J. D., Hanson, B. M., Neal, S. A., Tiegs, A. W., Osman, E. K., Scott, R., Lathi, R. B. ELSEVIER SCIENCE INC. 2019: E151

    View details for DOI 10.1016/j.fertnstert.2019.07.513

    View details for Web of Science ID 000487821301136

  • INCREASED PATERNAL AGE IS ASSOCIATED WITH DECREASED BLASTULATION AND EUPLOID RATES BUT NOT PREGNANCYOUTCOMES IN THE SETTING OF A EUPLOID SINGLE EMBRYO TRANSFER. Hanson, B. M., Kim, J. G., Osman, E. K., Tiegs, A. W., Neal, S. A., Lathi, R. B., Scott, R., Franasiak, J. M. ELSEVIER SCIENCE INC. 2019: E142?E143

    View details for DOI 10.1016/j.fertnstert.2019.07.493

    View details for Web of Science ID 000487821301116

  • Anti-Mullerian hormone in association with euploid embryo transfer outcomes. Reproductive biomedicine online Wang, A., Lathi, R., Kort, J., Westphal, L. 2019

    Abstract

    RESEARCH QUESTION: To investigate the association between anti-Mullerian hormone (AMH) concentration and maternal age with single euploid cryopreserved embryo transfer.DESIGN: Retrospective cohort study from 2014 to 2018 at an academic medical centre, including 389 cycles of IVF with 24-chromosome Day 5/6 preimplantation genetic testing for aneuploidies (PGT-A). Multivariate logistic regression was used to study AMH and age in relation to IVF outcomes (positive beta human chorionic gonadotrophin [bHCG], ongoing pregnancy and pregnancy loss rates) for patients with at least one euploid embryo for transfer, controlling for patient and cycle confounders.RESULTS: In this cohort the overall unadjusted positive bHCG rate was 69.2% and ongoing pregnancy rate was 52.7% per transfer, while the pregnancy loss rate was 23.4% per cycle with positive bHCG. Multivariate analysis found that compared with the reference group of AMH 1 to <5 ng/ml, AMH <1 and 5+ did not have any significant difference in positive bHCG (odds ratio, OR 0.65 [0.30-1.44] and 1.27 [0.61-2.65] for AMH <1 and AMH 5+, respectively) or ongoing pregnancy (OR 0.80 [0.43-1.50] and 1.41 [0.68-2.90]). However, AMH <1 had statistically significant lower euploid miscarriage rates compared with the reference group with OR 0.32 (0.12-0.85, P?=?0.022); AMH 5+ did not have any statistical difference in miscarriage rate. Neither age at retrieval nor age at transfer were significantly associated with transfer outcomes.CONCLUSIONS: AMH concentration was not associated with positive bHCG or ongoing pregnancy for euploid embryo transfers after adjustment for potential confounders. Maternal age was not associated with euploid transfer outcomes. Further study is warranted in larger cohorts.

    View details for DOI 10.1016/j.rbmo.2019.05.006

    View details for PubMedID 31395517

  • Increased risk of incident chronic medical conditions in infertile women: analysis of US claims data Murugappan, G., Li, S., Lathi, R. B., Baker, V. L., Eisenberg, M. L. MOSBY-ELSEVIER. 2019

    View details for DOI 10.1016/j.ajog.2019.01.214

    View details for Web of Science ID 000467043800012

  • Risk of cancer in infertile women: analysis of US claims data HUMAN REPRODUCTION Murugappan, G., Li, S., Lathi, R. B., Baker, V. L., Eisenberg, M. L. 2019; 34 (5): 894?902

    View details for DOI 10.1093/humrep/dez018

    View details for Web of Science ID 000484054400014

  • KARYOTYPE OF FIRST MISCARRIAGE IS PROGNOSTIC OF SUBSEQUENT PREGNANCY OUTCOME. Murugappan, G., Vyas, N. M., Lathi, R. B. ELSEVIER SCIENCE INC. 2019: E11?E12

    View details for DOI 10.1016/j.fertnstert.2019.02.048

    View details for Web of Science ID 000463487700012

  • Risk of cancer in infertile women: analysis of us claims data. Human reproduction (Oxford, England) Murugappan, G., Li, S., Lathi, R. B., Baker, V. L., Eisenberg, M. L. 2019

    Abstract

    STUDY QUESTION: Is female infertility associated with higher risk of cancer?SUMMARY ANSWER: Although absolute risks are low, infertility is associated with higher risk of cancer compared to a group of non-infertile women.WHAT IS KNOWN ALREADY: Infertile women are at higher risk of hormone-sensitive cancers. Information on risk of non-gynecologic cancers is rare and conflicting, and the effect of pregnancy on these risk associations is known for only a minority of cancer types.STUDY DESIGN, SIZE, DURATION: Retrospective cohort analysis between 2003 and 2016 using an insurance claims database.PARTICIPANTS/MATERIALS, SETTING, METHODS: In all, 64 345 infertile women identified by infertility diagnosis, testing or treatment were compared to 3 128 345 non-infertile patients seeking routine gynecologic care. Women with prior diagnosis of cancer or within 6 months of index event were excluded. Main outcomes were development of any malignancy and individual cancers as identified by ICD-9/ICD-10 codes. Results were adjusted for age at index date, index year, nulliparity, race, smoking, obesity, number of visits per year and highest level of education.MAIN RESULTS AND THE ROLE OF CHANCE: Infertile women had an overall higher risk of developing cancer compared to non-infertile women (2.0 versus 1.7%, adjusted hazard ratio (aHR) = 1.18; CI: 1.12-1.24). In addition, the risk of uterine cancer (0.10 versus 0.06%, aHR = 1.78; CI: 1.39-2.28), ovarian cancer (0.14 versus 0.09%, aHR 1.64; CI: 1.33-2.01), lung cancer (0.21 versus 0.21%, aHR = 1.38; CI: 1.01-1.88), thyroid cancer (0.21 versus 0.16%, aHR = 1.29; CI: 1.09-1.53), leukemia (0.10 versus 0.06%, aHR = 1.55; CI: 1.21-1.98) and liver and gallbladder cancer (0.05 versus 0.03%, aHR = 1.59; CI: 1.11-2.30) were higher in infertile women compared to non-infertile women. In a subgroup analysis of women in each cohort who became pregnant and had a delivery during enrollment, the risk of uterine and ovarian cancer were similar between infertile and non-infertile women. In a subgroup analysis excluding women with PCOS and endometriosis from both cohorts, the risk of uterine cancer was similar between infertile and non-infertile women.LIMITATIONS, REASONS FOR CAUTION: Absolute risk of cancer was low, average follow up for each individual was limited, and average age at index date was limited. Insurance databases have known limitations.WIDER IMPLICATIONS OF THE FINDINGS: Using claims-based data, we report that infertile women may have a higher risk of certain cancers in the years after infertility evaluation; continued follow up should be considered after reproductive goals are achieved.STUDY FUNDING/COMPETING INTEREST(S): None.

    View details for PubMedID 30863841

  • Increased Risk of Incident Chronic Medical Conditions in Infertile Women: Analysis of Us Claims Data. American journal of obstetrics and gynecology Murugapppan, G., Li, S., Lathi, R. B., Baker, V. L., Eisenberg, M. L. 2019

    Abstract

    BACKGROUND: The risk of common chronic medical conditions among infertile women is not known.OBJECTIVE: To study the association between female infertility and risk of incident chronic disease.STUDY DESIGN: Retrospective cohort analysis using the Optum de-identified Clinformatics© Datamart from 2003-2016. 64,345 infertile women were identified by infertility diagnosis, testing or treatment and compared to 3,128,345 non-infertile patients seeking routine gynecologic care. Women with prior diagnosis of the relevant chronic disease or cancer or with either diagnosis within six months of index event were excluded. Main outcome was diagnosis of incident chronic disease as identified by ICD-9/ICD-10 codes. Results were adjusted for age, index year, nulliparity, race, smoking, obesity, number of visits per year and highest level of education.RESULTS: Infertile patients were more likely to develop diabetes (aHR 1.44, CI 1.38-1.49), renal disease (aHR 1.22, CI 1.12-1.32), liver disease (aHR 1.25, CI 1.20-1.30), cerebrovascular disease (aHR 1.26, CI 1.15-1.38), ischemic heart disease (aHR 1.16, CI 1.09-1.24), other heart disease (aHR 1.16, CI 1.12-1.20), and drug abuse (aHR 1.24, CI 1.15-1.33) compared to non-infertile patients. Infertile patients were significantly less likely to develop alcohol abuse (aHR 0.86, CI 0.79-0.95) compared to non-infertile patients. Risk associations were similar after excluding women with PCOS and POI. In subgroup analyses of women who underwent pregnancy and childbirth during enrollment, several previously noted risk associations were attenuated compared to the overall cohort.CONCLUSION: While the absolute risk of chronic disease is low, infertility is associated with increased risk of incident chronic disease compared to a group of non-infertile women.

    View details for PubMedID 30710512

  • Antimullerian hormone is a predictor of live birth in patients with recurrent pregnancy loss. Fertility research and practice Murugappan, G., Shahine, L., Lathi, R. B. 2019; 5: 2

    Abstract

    Background: Ovarian reserve testing is not routinely performed in the evaluation of recurrent pregnancy loss (RPL). The objective of this study was to determine if AMH levels are predictive of live birth rate in RPL patients pursuing expectant management (EM).Methods: Retrospective cohort study of RPL patients. Patients tried to conceive spontaneously for 12 calendar months or until they achieved a live birth, whichever occurred first. All patients with the intent to conceive were included regardless of final outcome.Results: One hundred fifty-five RPL patients treated from 2009 to 2017 were included. In a univariate logistic regression, AMH<1ng/mL was associated with decreased likelihood of live birth (OR 0.38; CI 0.16-0.87, p=0.03) and increasing age (OR 0.91; CI 0.83-0.99, p=0.04). Likelihood of live birth was not significantly associated with BMI (OR 1.21; CI 0.83-1.77, p=0.31), three or four or more prior pregnancy losses (OR 0.93; CI 0.40-2.22, p=0.87 and OR 0.52; CI 0.19-1.42, p=0.20, respectively) and prior live births (OR 1.00; CI 0.48-2.08, p=0.99). AMH <1ng/mL was shown to be a stronger predictor of live birth than age using a multivariate model adjusting for age, AMH, and time to conception.Conclusions: AMH<1ng/mL is associated with decreased likelihood of live birth among RPL patients pursuing EM, and may be a stronger predictor of live birth than age in this population.

    View details for DOI 10.1186/s40738-019-0054-z

    View details for PubMedID 30923623

  • Miscarriage chromosome testing: Indications, benefits and methodologies. Seminars in perinatology McQueen, D. B., Lathi, R. B. 2018

    Abstract

    Rapid advances in genomics have expanded the use of chromosome testing following miscarriage. In addition to conventional cytogenetics, the availability of single nucleotide polymorphism microarray technology and array comparative geneomic hybridization have provided further options for clinicians. This review will cover the indications for testing and the advantages/disadvantages of the various methodologies available.

    View details for PubMedID 30638881

  • Are blastocyst aneuploidy rates different between fertile and infertile populations? JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Kort, J. D., McCoy, R. C., Demko, Z., Lathi, R. B. 2018; 35 (3): 403?8

    Abstract

    This study aimed to determine if patients with infertility or recurrent pregnancy loss have higher rates of embryo aneuploidy than fertile controls.This was a retrospective review of all pre-implantation genetic screening (PGS) cases processed by a single reference lab prior to March 2014 after a blastocyst biopsy. Cases were excluded if no indication for PGS was designated or patients were translocation carriers. The fertile control group consisted of patients undergoing IVF with PGS for sex selection only. The comparison cohorts included those with recurrent pregnancy loss, male factor infertility, unexplained infertility, prior failed IVF, or previous aneuploid conceptions. A quasi-binomial regression model was used to assess the relationship between the dependent variable, aneuploidy rate and the independent variables, maternal age and reason for PGS. A quasi-Poisson regression model was used to evaluate the relationship between similar independent variables and the number of blastocyst biopsies per case.The initial study population consisted of 3378 IVF-PGS cycles and 18,387 analyzed trophectoderm samples. Controlling for maternal age, we observed an increased rate of aneuploidy among patients with recurrent pregnancy loss (OR 1.330, p < 0.001), prior aneuploid pregnancy (OR 1.439, p < 0.001), or previous failed IVF cycles (OR 1.356, p = 0.0012) compared to fertile controls. Patients with unexplained and male factor infertility did not have a significantly different aneuploidy rate than controls (p > 0.05). The increase in aneuploidy in patients with RPL and prior IVF failure was driven by both an increase in meiotic (OR 1.488 and 1.508, p < 0.05) and mitotic errors (1.269 and 1.393, p < 0.05) relative to fertile controls, while patients with prior aneuploid pregnancies had only an increased risk of meiotic error aneuploidies (OR 1.650, p < 0.05).Patients with recurrent pregnancy loss, previous IVF failures, and prior aneuploid pregnancies have a significantly higher, age-independent, aneuploidy rate compared to patients without infertility.

    View details for PubMedID 29063503

    View details for PubMedCentralID PMC5904052

  • IS ANTIMULLERIAN HORMONE (AMH) PREDICTIVE OF REPRODUCTIVE POTENTIAL IN PATIENTS WITH RECURRENT PREGNANCY LOSS (RPL)? Murugappan, G., Shahine, L., Lathi, R. B. ELSEVIER SCIENCE INC. 2018: E39?E40

    View details for Web of Science ID 000427891800060

  • Comparison of cytogenetics and molecular karyotyping for chromosome testing of miscarriage specimens FERTILITY AND STERILITY Shah, M. S., Cinnioglu, C., Maisenbacher, M., Comstock, I., Kort, J., Lathi, R. B. 2017; 107 (4)

    Abstract

    To compare chromosome testing of miscarriage specimens between traditional cytogenetic analysis and molecular karyotyping using single nucleotide polymorphism microarrays (SNP) and array comparative genomic hybridization (aCGH).Prospective blinded cohort study.University-based practice.Women undergoing dilation and curettage for first-trimester miscarriage between March 2014 and December 2015.None.Chromosome analysis from chorionic villi separated equally and submitted for cytogenetics, SNP microarray, and aCGH testing.Sixty samples were analyzed, of which 47 (78%) were chromosomally abnormal. A correct call was defined when a result was concordant with at least one other testing platform. The correct call rate was 85%, 93%, and 85% using cytogenetics, SNP array, and aCGH, respectively. We found a 33% overall discordance rate between results. Discordances were due to maternal cell contamination, balanced chromosome rearrangements, polyploidy, and placental mosaicism. Mosaicism was detected in 18% of all samples. Growth failure occurred in four samples sent to cytogenetics, of which three were chromosomally abnormal by molecular testing.This study demonstrates the many technical limitations of the three testing modalities. Our rates of maternal cell contamination were low, but it is important to note that this is a commonly reported limitation of cytogenetics. Given the similar overall performance of the three testing modalities, providers may choose a method based on individual availability and consideration of limitations as it applies to each clinical scenario. The unexpected high rate of placental mosaicism warrants further investigation.

    View details for DOI 10.1016/j.fertnstert.2017.01.022

    View details for Web of Science ID 000400459100034

    View details for PubMedID 28283267

  • Warm reception for frozen embryos, but should a hot trend still be kept on ice? FERTILITY AND STERILITY Kort, J. D., Lathi, R. B., Baker, V. 2017; 107 (3): 575-576

    View details for DOI 10.1016/j.fertnstert.2017.01.004

    View details for Web of Science ID 000397985500012

    View details for PubMedID 28189297

  • Reply: The value of cytogenetic analysis of the product of conception before preimplantation genetic screening HUMAN REPRODUCTION Murugappan, G., Lathi, R. 2017; 32 (2): 479?80

    View details for PubMedID 27974444

  • Reply: PGS for recurrent pregnancy loss-still an open question HUMAN REPRODUCTION Murugappan, G., Lathi, R. 2017; 32 (2): 478?79

    View details for PubMedID 27974441

  • Caution: counseling patients with diminished ovarian reserve and recurrent pregnancy loss about in vitro fertilization with preimplantation genetic screening FERTILITY AND STERILITY Lathi, R. B., Kort, J. D. 2016; 106 (5): 1041?42

    View details for PubMedID 27473349

  • Control-matched surgical evaluation of endometriosis progression after IVF: a retrospective cohort study. Minerva ginecologica Crochet, P., Lathi, R. B., Dahan, M. H., Ocampo, J., Nutis, M., Nezhat, C. R. 2016; 68 (5): 481-486

    Abstract

    The aim of this study was to examine the surgical findings at repeated surgeries for endometriosis and to compare disease progression in patients after IVF to those without interval fertility treatments.A retrospective case-control study set at the referral center for gynecologic endoscopy at Stanford University. Women who had two surgeries for treatment of symptomatic endometriosis since 1997 were searched in the database. Twenty-one women were identified who underwent IVF treatment between the two procedures (IVF group), and compared to 36 women who did not receive any fertility treatment (controls). The main outcomes were time to recurrence and surgical findings including rASRM score. The presence and size of endometrioma, rectovaginal and para-rectal spaces location of endometriosis were also compared between the two surgical procedures.Demographics in the two groups were similar. The change in rASRM score between surgeries was not significantly different (P=0.80) between the two groups. There was no difference between the two groups in the size and number of pathology proven endometriomas as well as no difference in the presence of rectovaginal and pararectal endometriosis.No significant difference was found in the two groups, suggesting that IVF treatment does not lead to an accelerated progression of endometriosis in patients with recurrence.

    View details for PubMedID 26824508

  • Environmental exposure to endocrine-disrupting chemicals and miscarriage. Fertility and sterility Krieg, S. A., Shahine, L. K., Lathi, R. B. 2016; 106 (4): 941-947

    Abstract

    Establishment of early pregnancy is the result of complex biochemical interactions between the decidua and blastocyst. Any alteration in this chemical dialogue has the potential to result in adverse pregnancy outcomes including miscarriage. Sporadic miscarriage is the most common complication of pregnancy and can be caused by multiple factors. While the most common cause of miscarriage is genetic abnormalities in the fetus, other contributing factors certainly can play a role in early loss. One such factor is environmental exposure, in particular to endocrine-disrupting chemicals, which has the potential to interfere with endogenous hormone action. These effects can be deleterious, especially in early pregnancy when the hormonal milieu surrounding implantation is in delicate balance. The purpose of this paper is to review the current evidence on the role of environmental toxins in reproduction.

    View details for DOI 10.1016/j.fertnstert.2016.06.043

    View details for PubMedID 27473347

  • Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with recurrent pregnancy loss. Human reproduction Murugappan, G., Shahine, L. K., Perfetto, C. O., Hickok, L. R., Lathi, R. B. 2016; 31 (8): 1668-1674

    Abstract

    In an intent to treat analysis, are clinical outcomes improved in recurrent pregnancy loss (RPL) patients undergoing IVF and preimplantation genetic screening (PGS) compared with patients who are expectantly managed (EM)?Among all attempts at PGS or EM among RPL patients, clinical outcomes including pregnancy rate, live birth (LB) rate and clinical miscarriage (CM) rate were similar.The standard of care for management of patients with RPL is EM. Due to the prevalence of aneuploidy in CM, PGS has been proposed as an alternate strategy for reducing CM rates and improving LB rates.Retrospective cohort study of 300 RPL patients treated between 2009 and 2014.Among two academic fertility centers, 112 RPL patients desired PGS and 188 patients chose EM. Main outcomes measured were pregnancy rate and LB per attempt and CM rate per pregnancy. One attempt was defined as an IVF cycle followed by a fresh embryo transfer or a frozen embryo transfer (PGS group) and 6 months trying to conceive (EM group).In the IVF group, 168 retrievals were performed and 38 cycles canceled their planned PGS. Cycles in which PGS was intended but cancelled had a significantly lower LB rate (15 versus 36%, P = 0.01) and higher CM rate (50 versus 14%, P < 0.01) compared with cycles that completed PGS despite similar maternal ages. Of the 130 completed PGS cycles, 74% (n = 96) yielded at least one euploid embryo. Clinical pregnancy rate per euploid embryo transfer was 72% and LB rate per euploid embryo transfer was 57%. Among all attempts at PGS or EM, clinical outcomes were similar. Median time to pregnancy was 6.5 months in the PGS group and 3.0 months in the EM group.The largest limitation is the retrospective study design, in which patients who elected for IVF/PGS may have had different clinical prognoses than patients who elected for expectant management. In addition, the definition of one attempt at conception for PGS and EM groups was different between the groups and can introduce potential confounders. For example, it was not confirmed that patients in the EM group were trying to conceive for each month of the 6-month period.Success rates with PGS are limited by the high incidence of cycles that intend but cancel PGS or cycles that do not reach transfer. Counseling RPL patients on their treatment options should include not only success rates with PGS per euploid embryo transferred, but also LB rate per initiated PGS cycle. Furthermore, patients who express an urgency to conceive should be counseled that PGS may not accelerate time to conception.None.N/A.N/A.N/A.

    View details for DOI 10.1093/humrep/dew135

    View details for PubMedID 27278003

  • In vitro fertilization outcomes after fresh and frozen blastocyst transfer in South Asian compared with Caucasian women FERTILITY AND STERILITY Shah, M. S., Caballes, M., Lathi, R. B., Baker, V. L., Westphal, L. M., Milki, A. A. 2016; 105 (6): 1484-1487

    Abstract

    To study pregnancy outcomes between South Asian and Caucasian women undergoing frozen blastocyst transfer cycles.Retrospective cohort study.Not applicable.Caucasian and South Asian patients undergoing frozen blastocyst transfer between January 2011 and December 2014.Not applicable.Live birth rate.A total of 196 Caucasian and 117 South Asian women were included in our study. Indians were on average 2.2 years younger than Caucasian women (34.9 vs. 37.1 years), and were more likely to be nulliparous (59% vs. 43%). All other baseline characteristics were similar. In women undergoing their first frozen ET cycle, implantation rate (49% vs. 47%), clinical pregnancy rate (PR; 54% vs. 49%), and live birth rate (43% vs. 43%) were similar between South Asians and Caucasians, respectively. In patients who underwent a prior fresh blastocyst transfer, the live birth rate was significantly lower in South Asian versus Caucasian women (21% vs. 37%).Our data demonstrate that IVF outcomes are better in frozen versus fresh cycles among South Asian women. The IVF clinics may wish to consider these findings when counseling South Asian patients about the timing of ET.

    View details for DOI 10.1016/j.fertnstert.2016.02.027

    View details for PubMedID 26952781

  • Methotrexate does not affect ovarian reserve or subsequent assisted reproductive technology outcomes JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Boots, C. E., Hill, M. J., Feinberg, E. C., Lathi, R. B., Fowler, S. A., Jungheim, E. S. 2016; 33 (5): 647-656

    Abstract

    The purpose of this research was to study whether methotrexate (MTX) as treatment for ectopic pregnancy (EP) impacts the future fertility of women undergoing assisted reproductive technology (ART) METHODS: In a systematic review and multi-center retrospective cohort from four academic and private fertility centers, 214 women underwent an ART cycle before and after receiving MTX as treatment for an EP. Measures of ovarian reserve and responsiveness and rates of clinical pregnancy (CP) and live birth (LB) were compared in the ART cycles prior and subsequent to MTX.Seven studies were identified in the systematic review, and primary data from four institutions was included in the final analysis. Women were significantly older in post-MTX cycles (35.3 vs 34.7 years). There were no differences in follicle stimulating hormone, antral follicle count, duration of stimulation, oocytes retrieved, or fertilization rate between pre- and post-MTX cycles. However, post-MTX cycles received a significantly higher total dose of gonadotropins (4206 vs 3961 IU). Overall, 42 % of women achieved a CP and 35 % achieved a LB in the post-MTX ART cycle, which is similar to national statistics. Although no factors were identified that were predictive of LB in young women, the number of oocytes retrieved in the previous ART cycle and current AFC were predictive of LB (AUC 0.76, 0.75) for the older women.MTX does not influence ovarian reserve, response to gonadotropin stimulation, and CP or LB rate after ART. MTX remains a safe and effective treatment option for women with asymptomatic EPs.

    View details for DOI 10.1007/s10815-016-0683-7

    View details for PubMedID 26943917

    View details for PubMedCentralID PMC4870444

  • Patient Experience with Karyotyping After First Trimester Miscarriage A National Survey JOURNAL OF REPRODUCTIVE MEDICINE McNally, L., Diem Huynh, D., Keller, J., Dikan, J., Rabinowitz, M., Lathi, R. B. 2016; 61 (3-4): 128-132

    View details for Web of Science ID 000372860200006

  • Patient Experience with Karyotyping After First Trimester Miscarriage: A National Survey. journal of reproductive medicine McNally, L., Huynh, D., Keller, J., Dikan, J., Rabinowitz, M., Lathi, R. B. 2016; 61 (3-4): 128-132

    Abstract

    To assess the frequency of chromosome testing after first trimester miscarriage as well as to investigate patient experiences.An anonymous online questionnaire was developed and made available. Inclusion criteria were female, age ? 18, first trimester miscarriage, occurrence of miscarriage within the past year, miscarriage care provided in the United States, and survey completion.Of the 980 women who started the survey, 448 met inclusion criteria. Of those, 37 participants had chromosome testing on the miscarriage specimen. Of those who did not have testing, 66% said they wished they had done so at the time of miscarriage, and 67% said they would still want testing if it were available today. There was no correlation between patient age and chromosome testing. Chromosome testing increased in frequency with higher number of miscarriages, although the low number of women with chromosome testing limits our ability to draw definitive conclusions. On average, providers needed to spend 15-20 minutes with patients for them to feel like it was "enough time."In this national survey we found that chromosome testing is performed in approximately 8% of first trimester miscarriages. Our data indicate that the majority of patients experiencing first trimester miscarriage desire chromosome testing.

    View details for PubMedID 27172634

  • Pregnancy outcomes in women with chronic endometritis and recurrent pregnancy loss. Fertility and sterility McQueen, D. B., Perfetto, C. O., Hazard, F. K., Lathi, R. B. 2015; 104 (4): 927-931

    Abstract

    To evaluate the prevalence of chronic endometritis (CE) in women with recurrent pregnancy loss (RPL) and compare pregnancy outcomes in women with and without CE.Case-control observational study.Academic fertility practice.Women with two or more pregnancy losses.Hematoxylin and eosin (H & E) staining was performed on all endometrial biopsies and plasma cells were identified by morphology. Immunohistochemical (IHC) staining for CD138 was later applied to all tissue samples. Charts were reviewed to evaluate the outcome of the next clinical intrauterine pregnancy.Miscarriage rate and live birth rate.A total of 107 women met inclusion criteria. The use of CD138 IHC staining resulted in a significantly higher prevalence of CE compared with the use of H & E staining and morphological assessment alone (56% [60/107] vs. 13% [14/107]). The 51 women with untreated CE were compared with the 45 women without CE by CD138 staining. Among those women with a subsequent pregnancy, the live birth rate in the next clinical intrauterine pregnancy after endometrial evaluation was 67.6% (23/34) in women with untreated CE and 87.1% (27/31) in women without CE. Age, body mass index (BMI), results of RPL evaluation, and number of prior losses were not significantly different between the two groups.CD138 IHC staining of endometrial biopsies in women with RPL provides increased sensitivity when screening for CE compared with H & E staining and morphological assessment alone. Untreated CE may contribute to poor pregnancy outcomes and deserves further investigation in a larger cohort.

    View details for DOI 10.1016/j.fertnstert.2015.06.044

    View details for PubMedID 26207958

  • Increased body mass index negatively impacts blastocyst formation rate in normal responders undergoing in vitro fertilization JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Comstock, I. A., Kim, S., Behr, B., Lathi, R. B. 2015; 32 (9): 1299-1304

    Abstract

    The aim of this study is to investigate the effect of female BMI and metabolic dysfunction on blastocyst formation rate.This was a retrospective cohort study that was performed in an academic center for reproductive medicine. Patients who were normal weight, overweight with metabolic dysfunction, or obese who had ?6 oocytes retrieved in a fresh IVF cycle were included in the study. The blastocyst formation rate was calculated from the number of ?5 cell embryos on day 3 observed in culture until day 5 or day 6. Only good quality blastocysts were included in the calculation as defined by a morphologic grade of 3BB or better.The blastocyst formation rate was significantly better in the normal-weight controls versus overweight/obese patients (57.2 versus 43.6 %, p?

    View details for DOI 10.1007/s10815-015-0515-1

    View details for Web of Science ID 000362519600002

    View details for PubMedID 26109331

    View details for PubMedCentralID PMC4595387

  • Frozen blastocyst embryo transfer using a supplemented natural cycle protocol has a similar live birth rate compared to a programmed cycle protocol JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Lathi, R. B., Chi, Y., Liu, J., Saravanabavanandhan, B., Hegde, A., Baker, V. L. 2015; 32 (7): 1057-1062

    Abstract

    The purpose of this study is to compare outcomes for a supplemented natural cycle with a programmed cycle protocol for frozen blastocyst transfer.A retrospective analysis was performed of frozen autologous blastocyst transfers, at a single academic fertility center (519 supplemented natural cycles and 106 programmed cycles). Implantation, clinical pregnancy, miscarriage, and live birth and birth weight were compared using Pearson's Chi-squared test, T-test, or Fisher's exact test.There was no significant difference between natural and programmed frozen embryo transfers with respect to implantation (21.9 vs. 18.1 %), clinical pregnancy (35.5 vs. 29.2 %), and live birth rates (27.7 vs. 23.6 %). Mean birth weights were also similar between natural and programmed cycles for singletons (3354 vs. 3340 g) and twins (2422 vs. 2294 g)Frozen blastocyst embryo transfers using supplemented natural or programmed protocols experience similar success rates. Patient preference should be considered in choosing a protocol.

    View details for DOI 10.1007/s10815-015-0499-x

    View details for Web of Science ID 000359454000008

    View details for PubMedID 26018319

    View details for PubMedCentralID PMC4531857

  • Aneuploidy rates and blastocyst formation after biopsy of morulae and early blastocysts on day 5. Journal of assisted reproduction and genetics Kort, J. D., Lathi, R. B., Brookfield, K., Baker, V. L., Zhao, Q., Behr, B. R. 2015; 32 (6): 925-930

    Abstract

    Studies have demonstrated high implantation rates after trophectoderm biopsy of day 5 expanded blastocysts. However, biopsy of cleavage stage embryos may adversely affect embryo development and implantation. No studies have assessed the utility of day 5 morulae and early blastocyst biopsy. This study sought to better understand these slower embryos' aneuploidy rates and implantation potential.This was a retrospective review of all autologous IVF cycles utilizing PGS at a single academic infertility center.The biopsy of day 5 morulae and early blastocysts provided 22 % additional euploid blastocysts available for fresh day 6 transfer compared to day 5 biopsy of only expanded blastocysts. Aneuploidy did correlate with embryo stage on day 5, even after controlling for maternal age, with 16 % of morulae and 35 % of blastocysts being euploid. The majority (83 %) of euploid morulae progressed to the blastocyst stage by day 6. Experience transferring slower developing embryos is limited, but preliminary pregnancy and implantation rates appear similar to euploid embryos biopsied as expanded blastocysts.The biopsy of all non-arrested embryos on day 5 provides genetic information for all blastocysts on day 6, increasing the pool of euploid blastocysts available for fresh transfer and avoiding the need to cryopreserve developmentally competent embryos without genetic information.

    View details for DOI 10.1007/s10815-015-0475-5

    View details for PubMedID 25921084

    View details for PubMedCentralID PMC4491071

  • Expression of interleukin-22 in decidua of patients with early pregnancy and unexplained recurrent pregnancy loss. Journal of assisted reproduction and genetics Perfetto, C. O., Fan, X., Dahl, S., Krieg, S., Westphal, L. M., Lathi, R. B., Nayak, N. R. 2015; 32 (6): 977-984

    Abstract

    Researchers have hypothesized that an imbalance of immune cells in the uterine decidua and a dysfunction in cytokines they produce may contribute to recurrent pregnancy loss (RPL). The objective of this study was to determine if IL-22, IL-23 and IL-17 are expressed abnormally in the decidua of patients with RPL compared to those women with a normal pregnancy. We also sought to confirm that uterine natural killer (uNK) cells are lower in the decidua of patients with RPL, as well as identify IL-22 expression by uNK cells.After meeting strict inclusion criteria, maternal decidua of nine patients with unexplained RPL and a confirmed euploid fetal loss, and 11 gestational age-matched patients undergoing elective pregnancy termination were included in our analysis. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression, Western blot was performed to quantify protein expression and immunohistochemistry (IHC) was performed to identify IL-22 and uNK cells.We found that women with unexplained RPL and a euploid fetal loss had significantly less gene and protein expression of IL-22 in the decidua. Additionally, we found that IL-22 is primarily expressed by uNK cells in the decidua.In conclusion, our results suggest that lower levels of IL-22 in the uterine decidua in patients with unexplained RPL may contribute to a disruption of decidual homeostasis and ultimately lead to early pregnancy loss.

    View details for DOI 10.1007/s10815-015-0481-7

    View details for PubMedID 25925347

    View details for PubMedCentralID PMC4491088

  • Expression of interleukin-22 in decidua of patients with early pregnancy and unexplained recurrent pregnancy loss. Journal of assisted reproduction and genetics O'Hern Perfetto, C., Fan, X., Dahl, S., Krieg, S., Westphal, L. M., Bunker Lathi, R., Nayak, N. R. 2015; 32 (6): 977-984

    Abstract

    Researchers have hypothesized that an imbalance of immune cells in the uterine decidua and a dysfunction in cytokines they produce may contribute to recurrent pregnancy loss (RPL). The objective of this study was to determine if IL-22, IL-23 and IL-17 are expressed abnormally in the decidua of patients with RPL compared to those women with a normal pregnancy. We also sought to confirm that uterine natural killer (uNK) cells are lower in the decidua of patients with RPL, as well as identify IL-22 expression by uNK cells.After meeting strict inclusion criteria, maternal decidua of nine patients with unexplained RPL and a confirmed euploid fetal loss, and 11 gestational age-matched patients undergoing elective pregnancy termination were included in our analysis. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression, Western blot was performed to quantify protein expression and immunohistochemistry (IHC) was performed to identify IL-22 and uNK cells.We found that women with unexplained RPL and a euploid fetal loss had significantly less gene and protein expression of IL-22 in the decidua. Additionally, we found that IL-22 is primarily expressed by uNK cells in the decidua.In conclusion, our results suggest that lower levels of IL-22 in the uterine decidua in patients with unexplained RPL may contribute to a disruption of decidual homeostasis and ultimately lead to early pregnancy loss.

    View details for DOI 10.1007/s10815-015-0481-7

    View details for PubMedID 25925347

    View details for PubMedCentralID PMC4491088

  • Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss FERTILITY AND STERILITY Murugappan, G., Ohno, M. S., Lathi, R. B. 2015; 103 (5): 1215-1220

    Abstract

    To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL).Decision analytic model comparing costs and clinical outcomes.Academic recurrent pregnancy loss programs.Women with unexplained RPL.IVF/PGS with 24-chromosome screening and expectant management.Cost per live birth.The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing $45,300 per live birth compared with $418 per live birth with expectant management.In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management.

    View details for DOI 10.1016/j.fertnstert.2015.02.012

    View details for Web of Science ID 000353843700024

    View details for PubMedID 25772770

  • Pregnancy outcomes following 24-chromosome preimplantation genetic diagnosis in couples with balanced reciprocal or Robertsonian translocations FERTILITY AND STERILITY Idowu, D., Merrion, K., Wemmer, N., Mash, J. G., Pettersen, B., Kijacic, D., Lathi, R. B. 2015; 103 (4): 1037-1042

    Abstract

    To report live birth rates (LBR) and total aneuploidy rates in a series of patients with balanced translocations who pursued in vitro fertilization (IVF)-preimplantation genetic diagnosis (PGD) cycles.Retrospective cohort analysis.Genetic testing reference laboratory.Seventy-four couples who underwent IVF-PGD due to a parental translocation.IVF cycles and embryo biopsies were performed by referring clinics. Biopsy samples were sent to a single reference lab for PGD for the translocation plus 24-chromosome aneuploidy screening with the use of a single-nucleotide polymorphism (SNP) microarray.LBR per biopsy cycle, aneuploidy rate, embryo transfer (ET) rate, miscarriage rate.The LBR per IVF biopsy cycle was 38%. LBR for patients reaching ET was 52%. Clinical miscarriage rate was 10%. Despite a mean age of 33.8 years and mean of 7 embryos biopsied, there was a 30% chance for no chromosomally normal embryos. Maternal age >35 years, day 3 biopsy, and having fewer than five embryos available for biopsy increased the risk of no ET.IVF-PGD for translocation and aneuploidy screening had good clinical outcomes. Patients carrying a balanced translocation who are considering IVF-PGD should be aware of the high risk of no ET, particularly in women ?35 years old.

    View details for DOI 10.1016/j.fertnstert.2014.12.118

    View details for Web of Science ID 000352110400032

    View details for PubMedID 25712573

  • Recurrent Pregnancy Loss Evaluation and Treatment OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA Shahine, L., Lathi, R. 2015; 42 (1): 117-?

    Abstract

    Recurrent pregnancy loss (RPL) is a multifactorial condition. Approximately half of patients with RPL will have no explanation for their miscarriages. De novo chromosome abnormalities are common in sporadic and recurrent pregnancy loss. Testing for embryonic abnormalities can provide an explanation for the miscarriage in many cases and prognostic information. Regardless of the cause of RPL, patients should be reassured that the prognosis for live birth with an evidence-based approach is excellent for most patients. The authors review current evidence for the evaluation and treatment of RPL and explore the proposed use of newer technology for patients with RPL.

    View details for DOI 10.1016/j.ogc.2014.10.002

    View details for Web of Science ID 000350936900011

    View details for PubMedID 25681844

  • Time to next pregnancy in spontaneous pregnancies versus treatment cycles in fertile patients with recurrent pregnancy loss. Fertility research and practice Perfetto, C. O., Murugappan, G., Lathi, R. B. 2015; 1: 5

    Abstract

    BACKGROUND: The current standard of care for management of patients with recurrent pregnancy loss is expectant management. However, the emotional impact of pregnancy losses and the urgency to conceive often leads couples to consider a variety of fertility treatments. The objective of this study is to report the time to next pregnancy and subsequent live birth and miscarriage rates in fertile patients with recurrent pregnancy loss (RPL) who choose to attempt spontaneous conception compared to those that opt to pursue fertility treatment.METHODS: Retrospective cohort study of one hundred and fifty-eight fertile RPL patients treated at a university-based fertility center. Patients were followed for a minimum of 6months. Patients were encouraged to attempt spontaneous conception, but allowed to initiate fertility treatments (ovarian stimulation, insemination, IVF or PGS) according to their preferences. Main outcome measures were time to next pregnancy and pregnancy outcome.RESULTS: For those patients who achieved a spontaneous conception, 88% conceived within 6months, with a median time of 2months and range of 1-10 months. Patients using IUI, IVF and PGS conceived in a median of 3, 4 and 5months, respectively. The live birth rate and clinical miscarriage rate was not improved with any fertility treatment.CONCLUSIONS: In the fertile RPL patient population, there does not appear to be a benefit to proceeding directly with fertility treatment. Patients should be encouraged to attempt spontaneous conception for at least 6months.

    View details for PubMedID 28620510

  • Separation of miscarriage tissue from maternal decidua for chromosome analysis FERTILITY AND STERILITY Murugappan, G., Gustin, S., Lathi, R. B. 2014; 102 (4): E9-E10

    Abstract

    To demonstrate a technique for separation of miscarriage tissue from maternal decidua to reduce maternal cell contamination for chromosome analysis.Retrospective.University-based infertility center.Not applicable.Retrospective collection of de-identified images and video from manual vacuum aspiration (MVA) performed after first-trimester pregnancy losses. This project was exempt from institutional review board approval as no patient-identifying data were used.Reduction of maternal cell contamination and improvement of the accuracy of chromosome analysis.Video demonstration of separation of miscarriage tissue from maternal decidua after MVA.Chromosome analysis of a miscarriage is performed to assess the etiology of miscarriage and recurrent pregnancy loss. However, maternal cell contamination can limit the accuracy. This video demonstrates a technique for separating miscarriage tissue from maternal decidua after MVA to reduce maternal cell contamination prior to sending tissue for analysis. The same technique has been used in our clinic with first-trimester dilation and curettage using mechanical suction.

    View details for DOI 10.1016/j.fertnstert.2014.07.006

    View details for Web of Science ID 000343108200001

  • The role of serum testosterone in early pregnancy outcome: a comparison in women with and without polycystic ovary syndrome. Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstétrique et gynécologie du Canada : JOGC Lathi, R. B., Dahan, M. H., Reynolds-May, M. F., Milki, A. A., Behr, B., Westphal, L. M. 2014; 36 (9): 811-816

    Abstract

    Hyperandrogenic conditions in women are associated with increased rates of miscarriage. However, the specific role of maternal testosterone in early pregnancy and its association with pregnancy outcome is unknown. The purpose of this study was to compare serum testosterone levels during early pregnancy in women with and without polycystic ovary syndrome (PCOS) who either had successful pregnancies or miscarried.We collected serum samples from women attending a university-based fertility centre at the time of their first positive serum beta human chorionic gonadotropin pregnancy test. The samples were subsequently assayed for total testosterone level. We used logistical regression modelling to control for PCOS diagnosis, BMI, and age.Total testosterone levels were available for 346 pregnancies, including 286 successful pregnancies and 78 first trimester miscarriages. We found no difference in total testosterone levels between women who subsequently had an ongoing pregnancy (mean concentration 3.6 ± 2.6 nmol/L) and women with a miscarriage (mean 3.6 ± 2.4 nmol/L). Using the Rotterdam criteria to identify women with PCOS, we also found no differences in serum testosterone between women who had ongoing pregnancies or miscarriages, either with PCOS (P = 0.176) or without PCOS (P = 0.561).Our findings show that early pregnancy testosterone levels do not predict pregnancy outcome, and they call into question the role of testosterone in causing miscarriage in populations of women with PCOS. Further research is needed to elucidate the normal progression of testosterone levels during pregnancy and to investigate further the relationship between PCOS and miscarriage.

    View details for PubMedID 25222360

  • Genomic Imbalance in Products of Conception Single-Nucleotide Polymorphism Chromosomal Microarray Analysis OBSTETRICS AND GYNECOLOGY Levy, B., Sigurjonsson, S., Pettersen, B., Maisenbacher, M. K., Hall, M. P., Demko, Z., Lathi, R. B., Tao, R., Aggarwal, V., Rabinowitz, M. 2014; 124 (2): 202-209

    Abstract

    To report the full cohort of identifiable anomalies, regardless of known clinical significance, in a large-scale cohort of postmiscarriage products-of-conception samples analyzed using a high-resolution single-nucleotide polymorphism (SNP)-based microarray platform. High-resolution chromosomal microarray analysis allows for the identification of visible and submicroscopic cytogenomic imbalances; the specific use of SNPs permits detection of maternal cell contamination, triploidy, and uniparental disomy.Miscarriage specimens were sent to a single laboratory for cytogenomic analysis. Chromosomal microarray analysis was performed using a SNP-based genotyping microarray platform. Results were evaluated at the cytogenetic and microscopic (greater than 10 Mb) and submicroscopic (less than 10 Mb) levels. Maternal cell contamination was assessed using information derived from fetal and maternal SNPs.Results were obtained on 2,389 of 2,392 specimens (99.9%) that were less than 20 weeks of gestation. Maternal cell contamination was identified in 528 (22.0%) specimens. The remaining 1,861 specimens were considered to be of true fetal origin. Of these, 1,106 (59.4%) showed classical cytogenetic abnormalities: aneuploidy accounted for 945 (85.4%), triploidy for 114 (10.3%), and structural anomalies or tetraploidy for the remaining 47 (4.2%). Of the 755 (40.6%) cases considered normal at the cytogenetic level, SNP chromosomal microarray analysis revealed a clinically significant copy number change or whole-genome uniparental disomy in 12 (1.6%) and three (0.4%) cases, respectively.Chromosomal microarray analysis of products-of-conception specimens yields a high diagnostic return. Using SNPs extends the scope of detectable genomic abnormalities and facilitates reporting "true" fetal results. This supports the use of SNP chromosomal microarray analysis for cytogenomic evaluation of miscarriage specimens when clinically indicated.III.

    View details for DOI 10.1097/AOG.0000000000000325

    View details for Web of Science ID 000341317600002

    View details for PubMedID 25004334

  • Conjugated bisphenol A in maternal serum in relation to miscarriage risk. Fertility and sterility Lathi, R. B., Liebert, C. A., Brookfield, K. F., Taylor, J. A., vom Saal, F. S., Fujimoto, V. Y., Baker, V. L. 2014; 102 (1): 123-128

    Abstract

    To examine the relationship between the maternal serum bisphenol A (BPA) concentration at the time of the missed menstrual cycle and miscarriage risk.Retrospective cohort of prospectively collected serum samples.Academic fertility center.Women presenting for early pregnancy monitoring with singleton pregnancies.Stored serum samples from 4 to 5 weeks' gestation analyzed for conjugated serum BPA concentrations.Live birth, miscarriage, and chromosome content of miscarriage.With the 115 women included in the study, there were 47 live births and 68 clinical miscarriages (46 aneuploid and 22 euploid). Median conjugated BPA concentrations were higher in the women who had miscarriages than in those who had live births (0.101 vs. 0.075 ng/mL). Women with the highest quartile of conjugated BPA had an increased relative risk of miscarriage (1.83; 95% CI, 1.14-2.96) compared with the women in the lowest quartile. We found a similar increase risk for both euploid and aneuploid miscarriages.Maternal conjugated BPA was associated with a higher risk of aneuploid and euploid miscarriage in this cohort. The impact of reducing individual exposure on future pregnancy outcomes deserves further study.

    View details for DOI 10.1016/j.fertnstert.2014.03.024

    View details for PubMedID 24746738

  • Twice-daily dosing of gonadotropins does not improve embryo quality during in vitro fertilization cycles in women with polycystic ovary syndrome, when compared to once-daily dosing: a pilot study ARCHIVES OF GYNECOLOGY AND OBSTETRICS Dahan, M. H., Lathi, R. B. 2014; 289 (5): 1113-1118

    Abstract

    To determine whether overexpression of the FSH receptor in polycystic ovary syndrome (PCOS) results in a relative deficiency of gonadotropins and poor oocyte and embryo quality during in vitro fertilization (IVF) cycles. Whether twice-daily dosing of gonadotropins could therefore result in improved embryo quality, by fixing this hypothesized relative deficiency of gonadotropins.Embryos generated at a university-based fertility center in women with PCOS were compared from twice-daily dosing to once-daily dosing of gonadotropins during IVF cycles. Oocyte and embryo quality was compared. A single patient's embryos were included in the analysis from only one IVF cycle and all embryos from that cycle were included. 254 embryos were compared.Twice-daily vs. once-daily dosing of gonadotropins does not improve embryo or oocyte quality in women with PCOS.The defect in response to gonadotropins in PCOS is most likely due to an inherent defect in the ovary and not a relative deficiency of gonadotropins due to overexpression of the FSH receptors. More studies are needed to confirm this finding.

    View details for DOI 10.1007/s00404-013-3095-2

    View details for Web of Science ID 000334518400031

    View details for PubMedID 24276425

  • A retrospective cohort study to evaluate the impact of meaningful weight loss on fertility outcomes in an overweight population with infertility FERTILITY AND STERILITY Kort, J. D., Winget, C., Kim, S. H., Lathi, R. B. 2014; 101 (5): 1400-1403

    Abstract

    To determine if meaningful weight loss (?10%) improved conception and live birth rates of overweight patients with infertility.A retrospective cohort study.Academic medical center.Overweight patients (body mass index ?25 kg/m(2); n = 52) being treated for infertility and referred for weight loss counseling.Patients were given a "meaningful" weight loss goal of 10%. They were followed by an endocrinologist who provided diet and exercise recommendations, metabolic screening, and pharmacologic intervention when indicated.Pregnancy rate, live birth rate, weight loss.Thirty-two percent of the patients achieved meaningful weight loss. Patients achieving meaningful weight loss had significantly higher conception (88% vs. 54%) and live birth rates (71% vs. 37%) than those who did not.Weight loss improves live birth rates in overweight patients with infertility. Health care providers should incorporate weight loss counseling when caring for overweight patients who plan to conceive.

    View details for DOI 10.1016/j.fertnstert.2014.01.036

    View details for Web of Science ID 000335504600043

    View details for PubMedID 24581574

  • Embryo selection with preimplantation chromosomal screening in patients with recurrent pregnancy loss. Seminars in reproductive medicine Shahine, L. K., Lathi, R. B. 2014; 32 (2): 93-99

    Abstract

    Recurrent pregnancy loss (RPL) is a multifactorial disorder which is often challenging for both patients and providers. Guidelines for the evaluation and treatment of patients with RPL include screening for uterine abnormalities, parental chromosomes, and antiphospholipid antibodies, but approximately half of RPL patients remain unexplained. The current recommendation for patients with unexplained RPL is expectant management which offers most patients a 60 to 80% success rate over time. Genetic imbalances in the embryo, including inherited unbalanced translocations and de novo aneuploidy, are frequent causes of miscarriage. Preimplantation genetic screening (PGS) has been proposed as an effective method for selecting viable embryos for transfer that may result lower risk of miscarriage for patients with unexplained RPL and carriers of balanced translocations. The current evidence examining the use of in vitro fertilization with PGS in patients with RPL reveals variable results, due to differences in technologies used and variable patient populations. Newer approaches, which include blastocyst biopsy and the ability to screen for all 24 chromosomes, show the most promise in reducing miscarriage rates. Studies that identify which patients are most likely to benefit from PGS and include live birth rates per initiated cycles are needed before universally recommending this treatment to couples with RPL.

    View details for DOI 10.1055/s-0033-1363550

    View details for PubMedID 24515903

  • Reliability of 46, XX results on miscarriage specimens: a review of 1,222 first-trimester miscarriage specimens FERTILITY AND STERILITY Lathi, R. B., Gustin, S. L., Keller, J., Maisenbacher, M. K., Sigurjonsson, S., Tao, R., Demko, Z. 2014; 101 (1): 178-182

    Abstract

    To examine the rate of maternal contamination in miscarriage specimens.Retrospective review of 1,222 miscarriage specimens submitted for chromosome testing with detection of maternal cell contamination (MCC).Referral centers requesting genetic testing of miscarriage specimens at a single reference laboratory.Women with pregnancy loss who desire complete chromosome analysis of the pregnancy tissue.Analysis of miscarriage specimens using single-nucleotide polymorphism (SNP) microarray technology with bioinformatics program to detect maternal cell contamination.Chromosome content of miscarriages and incidence of 46,XX results due to MCC.Of the 1,222 samples analyzed, 592 had numeric chromosomal abnormalities, and 630 were normal 46,XX or 46,XY (456 and 187, respectively). In 269 of the 46,XX specimens, MCC with no embryonic component was found. With the exclusion of maternal 46,XX results, the chromosomal abnormality rate increased from 48% to 62%, and the ratio for XX to XY results dropped from 2.6 to 1.0.Over half of the normal 46,XX results in miscarriage specimens were due to MCC. The use of SNPs in MCC testing allows for precise identification of chromosomal abnormalities in miscarriage as well as MCC, improving the accuracy of products of conception testing.

    View details for DOI 10.1016/j.fertnstert.2013.09.031

    View details for Web of Science ID 000329128800036

    View details for PubMedID 24182409

  • Frequency of the Male Infertility Evaluation: Data from the National Survey of Family Growth JOURNAL OF UROLOGY Eisenberg, M. L., Lathi, R. B., Baker, V. L., Westphal, L. M., Milki, A. A., Nangia, A. K. 2013; 189 (3): 1030-1034

    Abstract

    An estimated 7 million American couples per year seek infertility care in the United States. A male factor contributes to 50% of cases but it is unclear what proportion of infertile couples undergoes male evaluation.We analyzed data from cycles 5 to 7 of the National Survey of Family Growth performed by the Centers for Disease Control to determine the frequency of a male infertility evaluation, and associated reproductive and demographic factors.A total of 25,846 women and 11,067 men were surveyed. Male evaluation was not completed in 18% of couples when the male partner was asked vs 27% when female partners were asked. This corresponds to approximately 370,000 to 860,000 men in the population who were not evaluated at the time of infertility evaluation. Longer infertility duration and white race were associated with increased odds of male infertility evaluation. The male and female samples showed no change in the receipt of male examination with time.Many men from infertile couples do not undergo male evaluation in the United States. Given the potential implications to reproductive goals and male health, further examination of this pattern is warranted.

    View details for DOI 10.1016/j.juro.2012.08.239

    View details for PubMedID 23009868

  • Incidence of Chronic Endometritis and Subsequent Pregnancy Outcomes in Patients with Recurrent Pregnancy Loss 61st Annual Meeting of the Pacific-Coast-Reproductive-Society (PCRS) Perfetto, C. O., Hazard, F. K., Lathi, R. B. ELSEVIER SCIENCE INC. 2013: S11?S12

    View details for Web of Science ID 000315281800019

  • Outcomes of trophectoderm biopsy on cryopreserved blastocysts: a case series REPRODUCTIVE BIOMEDICINE ONLINE Lathi, R. B., Massie, J. A., Gilani, M., Milki, A. A., Westphal, L. M., Baker, V. L., Behr, B. 2012; 25 (5): 504-507

    Abstract

    Preimplantation genetic diagnosis (PGD) is an increasingly common adjunct to IVF. The information gained from PGD may be used to reduce the incidence of chromosomally abnormal pregnancies and augment the current selection process of embryos. As such, patients may choose to utilize PGD in either fresh or cryopreserved IVF cycles. It is a common practice to cryopreserve excess embryos at the blastocyst stage. In these cases, trophectoderm biopsy is the only technique available for PGD. This articles reports this study centre's experience with trophectoderm biopsies of cryopreserved blastocysts in 12 patients who underwent 13 cycles of PGD. The implantation rate per embryo transferred was 46% and the ongoing pregnancy rate per embryo transfer was 63%. The results from this case series demonstrate that trophectoderm biopsy on cryopreserved blastocysts to perform PGD is logistically feasible. In addition, the rate of implantation and ongoing pregnancy were maintained within a reasonable range to justify the procedure. Preimplantation genetic diagnosis (PGD) is an increasingly common adjunct to IVF and is used to evaluate the genetic makeup of the embryo prior to transfer of the embryo into the uterus. The information gained from PGD may be used to identify single-gene disorders that result in genetic disease, reduce the incidence of chromosomally abnormal pregnancies and/or augment the selection process of embryos to be transferred. In order to perform PGD, a biopsy of the embryo is the performed and cells are removed for testing. PGD may be performed in either fresh or frozen (cryopreserved) IVF cycles. Patients who have cryopreserved embryos remaining in storage from a previous fresh cycle may wish to have these embryos tested with PGD. Many embryos are frozen on day 5 of development, referred to as the blastocyst stage. At this stage of development, embryo biopsy is performed via a technique known as 'trophectoderm biopsy', in which 1-3 of the cells destined to become the placenta are removed from the embryo for chromosomal testing. We report our experience with trophectoderm biopsy of frozen blastocysts in 12 patients who underwent 13 cycles of PGD. The implantation rate per embryo transferred was 46% and the ongoing pregnancy rate per embryo transfer was 63%. The results from this case series demonstrate that trophectoderm biopsy on cryopreserved blastocysts to perform PGD is logistically feasible. In addition, the rate of implantation and ongoing pregnancy were maintained within a reasonable range to justify the procedure.

    View details for DOI 10.1016/j.rbmo.2012.06.021

    View details for Web of Science ID 000310639600010

    View details for PubMedID 22985500

  • Global alteration in gene expression profiles of deciduas from women with idiopathic recurrent pregnancy loss MOLECULAR HUMAN REPRODUCTION Krieg, S. A., Fan, X., Hong, Y., Sang, Q., Giaccia, A., Westphal, L. M., Lathi, R. B., Krieg, A. J., Nayak, N. R. 2012; 18 (9): 442-450

    Abstract

    Recurrent pregnancy loss (RPL) occurs in ?5% of women. However, the etiology is still poorly understood. Defects in decidualization of the endometrium during early pregnancy contribute to several pregnancy complications, such as pre-eclampsia and intrauterine growth restriction (IUGR), and are believed to be important in the pathogenesis of idiopathic RPL. We performed microarray analysis to identify gene expression alterations in the deciduas of idiopathic RPL patients. Control patients had one antecedent term delivery, but were undergoing dilation and curettage for current aneuploid miscarriage. Gene expression differences were evaluated using both pathway and gene ontology (GO) analysis. Selected genes were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A total of 155 genes were found to be significantly dysregulated in the deciduas of RPL patients (>2-fold change, P < 0.05), with 22 genes up-regulated and 133 genes down-regulated. GO analysis linked a large percentage of genes to discrete biological functions, including immune response (23%), cell signaling (18%) and cell invasion (17.1%), and pathway analysis revealed consistent changes in both the interleukin 1 (IL-1) and IL-8 pathways. All genes in the IL-8 pathway were up-regulated while genes in the IL-1 pathway were down-regulated. Although both pathways can promote inflammation, IL-1 pathway activity is important for normal implantation. Additionally, genes known to be critical for degradation of the extracellular matrix, including matrix metalloproteinase 26 and serine peptidase inhibitor Kazal-type 1, were also highly up-regulated. In this first microarray approach to decidual gene expression in RPL patients, our data suggest that dysregulation of genes associated with cell invasion and immunity may contribute significantly to idiopathic recurrent miscarriage.

    View details for DOI 10.1093/molehr/gas017

    View details for Web of Science ID 000308243000003

    View details for PubMedID 22505054

    View details for PubMedCentralID PMC3431184

  • Oocyte retrieval following continued stimulation five days beyond ovulation yields live birth after frozen embryo transfer JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Friedman, B. E., Pao, S., Westphal, L. M., Lathi, R. B. 2012; 29 (5): 433-435

    View details for DOI 10.1007/s10815-012-9721-2

    View details for Web of Science ID 000303881200011

    View details for PubMedID 22327896

    View details for PubMedCentralID PMC3348279

  • Informatics Enhanced SNP Microarray Analysis of 30 Miscarriage Samples Compared to Routine Cytogenetics PLOS ONE Lathi, R. B., Loring, M., Massie, J. A., Demko, Z. P., Johnson, D., Sigurjonsson, S., Gemelos, G., Rabinowitz, M. 2012; 7 (3)

    Abstract

    The metaphase karyotype is often used as a diagnostic tool in the setting of early miscarriage; however this technique has several limitations. We evaluate a new technique for karyotyping that uses single nucleotide polymorphism microarrays (SNP). This technique was compared in a blinded, prospective fashion, to the traditional metaphase karyotype.Patients undergoing dilation and curettage for first trimester miscarriage between February and August 2010 were enrolled. Samples of chorionic villi were equally divided and sent for microarray testing in parallel with routine cytogenetic testing.Thirty samples were analyzed, with only four discordant results. Discordant results occurred when the entire genome was duplicated or when a balanced rearrangement was present. Cytogenetic karyotyping took an average of 29 days while microarray-based karytoyping took an average of 12 days.Molecular karyotyping of POC after missed abortion using SNP microarray analysis allows for the ability to detect maternal cell contamination and provides rapid results with good concordance to standard cytogenetic analysis.

    View details for DOI 10.1371/journal.pone.0031282

    View details for Web of Science ID 000303017700008

    View details for PubMedID 22403611

    View details for PubMedCentralID PMC3293871

  • Testosterone concentrations in early pregnancy: relation to method of conception in an infertile population REPRODUCTIVE BIOMEDICINE ONLINE Lathi, R. B., Moayeri, S. E., Reddy, C. D., Gebhardt, J., Behr, B., Westphal, L. M. 2012; 24 (3): 360-363

    Abstract

    This prospective cohort study of infertility patients compared testosterone concentrations in early pregnancy in infertility patients who conceived naturally or after treatment. Although all groups demonstrated some increase in pregnancy testosterone from baseline concentrations, subjects who conceived following ovulation induction showed a significantly increased rise in testosterone as compared with controls (P<0.01).

    View details for DOI 10.1016/j.rbmo.2011.11.018

    View details for PubMedID 22285241

  • Characterization of Patient Recovery After First Trimester Miscarriage: Results From A National Survey 60th Annual Meeting of the Pacific-Coast-Reproductive-Society McNally, L., Lathi, R. B., Huynh, D., Keller, J., Dikan, J., Rabinowitz, M. ELSEVIER SCIENCE INC. 2012

    View details for Web of Science ID 000300876000066

  • Incidence of Endometritis in Recurrent Pregnancy Loss Patients 60th Annual Meeting of the Pacific-Coast-Reproductive-Society Perfetto, C. O., Lathi, R. B. ELSEVIER SCIENCE INC. 2012

    View details for Web of Science ID 000300876000022

  • Successful frozen blastocyst transfers after failed fresh transfers in assisted reproductive technologies patients with hydrosalpinx AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Sueldo, C. M., Milki, A. A., Lathi, R. B. 2012; 206 (3): E4-E6

    Abstract

    Untreated hydrosalpinx is known to decrease in vitro fertilization success. We report on 4 patients with hydrosalpinx for whom fresh transfers of 11 good quality embryos did not produce a pregnancy; however, frozen blastocyst transfers in natural cycles resulted in several successful pregnancies, with an implantation rate of 60% (9/15 blastocysts implanted).

    View details for DOI 10.1016/j.ajog.2011.12.020

    View details for Web of Science ID 000300878600002

    View details for PubMedID 22285169

  • Comparison of morbidity associated with laparoscopic myomectomy and hysterectomy for the treatment of uterine leiomyomas. Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstétrique et gynécologie du Canada : JOGC Lemyre, M., Bujold, E., Lathi, R., Bhagan, L., Huang, J. Q., Nezhat, C. 2012; 34 (1): 57-62

    Abstract

    To compare short-term morbidity and quality of life after laparoscopic hysterectomy (LH) and laparoscopic myomectomy (LM) for the treatment of symptomatic uterine leiomyomas.We performed a prospective, observational study of women who were eligible for both surgical procedures. After informed consent was obtained, each participant was asked to complete the SF-12v2 Health Survey before surgery and to repeat it seven days and 28 days after surgery. Data on short-term morbidities, such as operative time, blood loss, length of hospital stay, and surgical complications, were collected by an obstetrician-gynaecologist. Women who underwent LH were compared by non-parametric statistical analyses with those who underwent LM.Sixty-one women were recruited between January 1 and December 31, 2008, including 40 who underwent LM and 21 LH. Women who underwent LH were older, had higher parity, and were less likely to have infertility than those who chose LM. Median LH operative time of 223 minutes (IQR 214 to 241) was slightly longer than for LM (188 minutes, IQR 154 to 239; P = 0.02). However, we found no difference between the two groups in terms of SF-12v2 fluctuation, blood loss, hospital stay, and short-term complications.Laparoscopic myomectomy is a viable alternative to laparoscopic hysterectomy for women with symptomatic leiomyomas who want conservative surgery. The procedures have similar morbidity and impact on quality of life.

    View details for PubMedID 22260764

  • Early pregnancy testosterone after ovarian stimulation and pregnancy outcome FERTILITY AND STERILITY Gustin, S. L., Mukherjee, G., Baker, V. L., Westphal, L. M., Milki, A. A., Lathi, R. B. 2012; 97 (1): 23-U48

    Abstract

    To examine early pregnancy (EP) testosterone (T) after ovarian stimulation and its effect on singleton pregnancy outcomes.Prospective cohort study.University-based tertiary care center.Subfertile women who conceived with or without fertility treatment.Ovarian stimulation for assisted reproduction, collection of serum total T levels in early pregnancy, and pregnancy follow-up.Rate of preterm delivery, low birth weight (LBW) (<2,500 g), and hypertensive disorders of pregnancy.EP serum samples were measured from 266 singleton pregnancies. The mean T level among spontaneous conceptions was 74.90 ng/dL (SD 48.35 ng/dL); 103 ng/mL was the 90th percentile. Mean EP T was increased among patients who underwent ovarian stimulation compared with nonstimulated control subjects. In patients undergoing IVF, T levels in EP were linearly correlated with the number of oocytes retrieved. When pregnancy outcomes in women with normal T were compared with women with elevated T (>90th percentile), we did not see an increased risk for preterm delivery, hypertensive disorders of pregnancy, LBW infants, or cesarean delivery (odds ratio ratios 1.43, 0.38, 1.39, and 0.85, respectively).Elevations in EP T are associated with ovarian stimulation but do not appear to be associated with adverse pregnancy outcome. Further investigation to determine the etiology of increased maternal and neonatal morbidity among subfertile women is warranted.

    View details for DOI 10.1016/j.fertnstert.2011.10.020

    View details for PubMedID 22112646

  • First Trimester Miscarriage Evaluation SEMINARS IN REPRODUCTIVE MEDICINE Lathi, R. B., Hazard, F. K., Heerema-McKenney, A., Taylor, J., Chueh, J. T. 2011; 29 (6): 463-469

    Abstract

    Miscarriage is a relatively common occurrence for otherwise healthy women. Despite its frequency, evaluation for cause is rare. The most common cause of miscarriage is sporadic chromosome errors. Chromosomal analysis of the miscarriage offers an explanation in at least 50% of cases. Conventional cytogenetic evaluation can only be done on fresh tissue, so it is critical that the treating physician consider genetic testing at the time of the miscarriage. Ultrasound can estimate the gestational age at the time of miscarriage and identify major abnormalities in some embryos. A careful pathological examination can add to the evaluation by ruling out rare disorders with the highest recurrence risk. A multidisciplinary approach to miscarriage evaluation is essential to understanding the cause and risk of recurrence. A thorough evaluation of a miscarriage, in combination with emotional support, can often provide the necessary reassurance and confidence as the patient prepares for her next pregnancy.

    View details for DOI 10.1055/s-0031-1293200

    View details for PubMedID 22161459

  • PATIENT DESIRE FOR CHROMOSOME ANALYSIS OF PRODUCTS OF CONCEPTION FOLLOWING MISCARRIAGE: A NATIONAL SURVEY 67th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM) Lathi, R. B., Huynh, D., Keller, J., Dikan, J., Rabinowitz, M. ELSEVIER SCIENCE INC. 2011: S91?S91

    View details for Web of Science ID 000294452700308

  • Sextuplet heterotopic pregnancy presenting as ovarian hyperstimulation syndrome and hemoperitoneum FERTILITY AND STERILITY Fisher, S. L., Massie, J. A., Blumenfeld, Y. J., Lathi, R. B. 2011; 95 (7)

    Abstract

    To describe a case of bilateral ruptured heterotopic pregnancies presenting as persistent ovarian hyperstimulation syndrome in a quadruplet pregnancy.Case report.University hospital and clinic.An infertile patient who conceived using gonadotropin therapy.Culdocentesis with resultant aspiration of sanguinous fluid prompted laparoscopic exploration and bilateral salpingectomies.Not applicable.Gross hemoperitoneum and ruptured bilateral heterotopic sextuplet pregnancy.Patients who conceive after gonadotropin therapy should be closely monitored during treatment and in early pregnancy to recognize and minimize morbidity and complications. After superovulation, the presence of an intrauterine pregnancy, either single or multiple, does not rule out the possibility of ectopic pregnancy, and this should always be considered as a possibility in the setting of acute anemia.

    View details for DOI 10.1016/j.fertnstert.2011.01.172

    View details for Web of Science ID 000290791000088

    View details for PubMedID 21406303

  • The effect of air bubble position after blastocyst transfer on pregnancy rates in IVF cycles FERTILITY AND STERILITY Friedman, B. E., Lathi, R. B., Henne, M. B., Fisher, S. L., Milki, A. A. 2011; 95 (3): 944-947

    Abstract

    To investigate the relationship between air bubble position after blastocyst transfer (BT) and pregnancy rates (PRs).Retrospective cohort study.University-based infertility center.Three hundred fifteen consecutive nondonor BTs by a single provider.Catheters were loaded with 25 ?L of culture media, 20 ?L of air, 25 ?L of media containing the blastocysts, 20 ?L of air, and a small amount of additional media. The distance from the air bubble to the fundus, as seen on abdominal ultrasound examination, was measured at the time of transfer. Air bubble location was categorized as <10 mm, 10-20 mm, and >20 mm from the fundus.Clinical pregnancy rate.After controlling for age, parity, FSH and frozen transfers, and accounting for repeated cycles per patient, the PRs for both the >20-mm (38.3%) and the 10-20-mm (42.0%) from the fundus group were significantly reduced compared with the group in which the bubble was <10 mm from the fundus (62.5%).This study is the first to suggest that BT closer to the fundus is associated with higher PR. Although no ectopic pregnancies occurred in the <10-mm group, this outcome should be monitored closely in larger studies.

    View details for DOI 10.1016/j.fertnstert.2010.07.1063

    View details for Web of Science ID 000287480300019

    View details for PubMedID 20810105

  • Miscarriage Due to Sperm-Derived Embryonic Aneuploidy in the Setting of Recurrent Early Pregnancy Loss: A Case Report 59th Annual Meeting of the Pacific-Coast-Reproductive-Society Massie, J. A., Karpman, E., Lathi, R. B. ELSEVIER SCIENCE INC. 2011: S19?S19

    View details for Web of Science ID 000287733700040

  • Ovarian stimulation and the risk of aneuploid conceptions 64th Annual Meeting of the American-Society-for-Reproductive-Medicine Massie, J. A., Shahine, L. K., Milki, A. A., Westphal, L. M., Lathi, R. B. ELSEVIER SCIENCE INC. 2011: 970?72

    Abstract

    To examine the rate of aneuploidy in missed abortions in patients who conceived after FSH ovarian stimulation compared with women who conceived in a natural cycle.Retrospective cohort.Academic reproductive endocrinology and infertility center.Women with karyotyping of products of conception (POC) from a missed abortion from January 1999 through August 2007. The rate of aneuploidy was compared between patients with a history of infertility who conceived naturally and patients with a history of infertility who conceived with FSH treatment.Ovarian stimulation with FSH, intrauterine insemination, and in vitro fertilization; genetic testing of POC after dilation and curettage.Embryonic karyotype.A total of 229 pregnancies met inclusion criteria, and of these, 64% had an abnormal karyotype. The rate of aneuploidy was 63% in the study group and 70% in the control group. This difference was not statistically significant.The incidence of embryonic aneuploidy was not higher in pregnancies conceived with FSH stimulation compared with spontaneous conceptions in infertility patients. This suggests that exogenous FSH exposure does not increase the risk of aneuploidy.

    View details for DOI 10.1016/j.fertnstert.2010.07.1088

    View details for Web of Science ID 000287480300024

    View details for PubMedID 20828683

  • Age-Related Success with Elective Single versus Double Blastocyst Transfer. ISRN obstetrics and gynecology Friedman, B. E., Davis, L. B., Lathi, R. B., Westphal, L. M., Baker, V. L., Milki, A. A. 2011; 2011: 656204-?

    Abstract

    Background. Although the optimal outcome of assisted reproductive technology (ART) is a healthy singleton pregnancy, the rate of twin gestation from ART in women over the age of 35 is persistently high. Methods/Findings. We compared clinical pregnancy rates (PRs), ongoing pregnancy/live birth rates, and multiple gestation rates (MGRs) in 108 women who chose elective single blastocyst transfer (eSBT) to 415 women who chose elective double blastocyst transfer (eDBT) at a hospital-based IVF center. There was no significant difference in PR between eSBT and eDBT (57.4% versus 50.2%, P = 0.47) nor between eSBT and eDBT within each age group: <35, 35-37, 38-40, and >40. The risk of multiple gestations, however, was greatly increased between eSBT and eDBT (1.6 versus 32.4%, P < 0.00005), and this difference did not vary across age groups. Conclusion(s). Women undergoing eDBT are at uniformly high risk of multiple gestation regardless of age. eSBT appears to significantly lower the risk of multiple gestation without compromising PR.

    View details for DOI 10.5402/2011/656204

    View details for PubMedID 22191047

  • Day 2 versus day 3 embryo transfer in poor responders: a prospective randomized trial FERTILITY AND STERILITY Shahine, L. K., Milki, A. A., Westphal, L. M., Baker, V. L., Behr, B., Lathi, R. B. 2011; 95 (1): 330-332

    Abstract

    Day 2 embryo transfer has been suggested as a method to improve pregnancy rates in poor responders compared with day 3 transfer. Our prospective randomized controlled trial does not show a difference in outcomes based on day of embryo transfer.

    View details for DOI 10.1016/j.fertnstert.2010.06.093

    View details for PubMedID 20813357

  • Is infertility a risk factor for female sexual dysfunction? A case-control study FERTILITY AND STERILITY Millheiser, L. S., Helmer, A. E., Quintero, R. B., Westphal, L. M., Milki, A. A., Lathi, R. B. 2010; 94 (6): 2022-2025

    Abstract

    To determine the impact of infertility on female sexual function.A case-control study.Academic infertility and gynecology practices.One hundred nineteen women with infertility and 99 healthy female controls without infertility between the ages of 18 and 45 years were included in this study.Anonymous survey and Female Sexual Function Index.Female Sexual Function Index scores, frequency of sexual intercourse and masturbation, and sex-life satisfaction.Twenty-five percent of our control group had Female Sexual Function Index scores that put them at risk for sexual dysfunction (<26.55), whereas 40% of our patients with infertility met this criterion. Compared with the control group, the patients with infertility had significantly lower scores in the desire and arousal domains and lower frequency of intercourse and masturbation. The patients with infertility retrospectively reported a sex-life satisfaction score that was similar to that of the controls before their diagnosis, whereas their current sex-life satisfaction scores were significantly lower than those of the controls.Women with a diagnosis of infertility were found to be at higher risk for sexual dysfunction on the basis of their Female Sexual Function Index scores compared with women without infertility. The interaction of sexual function and infertility is complex and deserves further study.

    View details for DOI 10.1016/j.fertnstert.2010.01.037

    View details for PubMedID 20206929

  • Etiology of recurrent pregnancy loss in women over the age of 35 years 55th Annual Meeting of the Pacific-Coast-Reproductive-Society Marquard, K., Westphal, L. M., Milki, A. A., Lathi, R. B. ELSEVIER SCIENCE INC. 2010: 1473?77

    Abstract

    To determine the rate of embryonic chromosomal abnormalities, thrombophilias, and uterine anomalies in women over the age of 35 years with recurrent pregnancy loss (RPL).Retrospective cohort study.Academic reproductive endocrinology and infertility clinic.Women>or=35 years old with >or=3 first trimester miscarriages.None.Age, number of prior losses, cytogenetic testing of the products of conception (POC), uterine cavity evaluation, parental karyotype, TSH, and antiphospholipd antibody (APA) and thrombophilia testing. Aneuploidy in the POC in women with RPL was compared with sporadic miscarriages (or=35 years.Among 43 RPL patients, there were 50 miscarriages in which cytogenetic analysis was performed. In the RPL group, the incidence of chromosomal abnormalities in the POC was 78% (39 out of 50) compared with a 70% incidence (98 out of 140) in the sporadic losses. Thrombophilia results in the RPL patients were normal in 38 patients, four patients had APA syndrome, and one had protein C deficiency. Forty out of 43 had normal uterine cavities. Both TSH and parental karyotypes were normal in all of the patients tested. When the evaluation of RPL included karyotype of the POC, only 18% remained without explanation. However, without fetal cytogenetics, 80% of miscarriages would have been unexplained.In older patients with RPL, fetal chromosomal abnormalities are responsible for the majority of miscarriages. Other causes were present in only 20% of cases.

    View details for DOI 10.1016/j.fertnstert.2009.06.041

    View details for Web of Science ID 000281674600051

    View details for PubMedID 19643401

  • PERSONALIZED PREDICTION OF LIVE BIRTH OUTCOMES IN IVF. 66th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM) Banerjee, P., Choi, B., Lathi, R. B., Westphal, L. M., Wong, W. H., Yao, M. W. ELSEVIER SCIENCE INC. 2010: S52?S53

    View details for Web of Science ID 000281441000180

  • CHARACTERIZATION OF A RECURRENT PREGNANCY LOSS GENE EXPRESSION SIGNATURE IN PERIPHERAL BLOOD LEUKOCYTES (PBL). 66th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM) Maas, K. H., Krieg, S., Dosiou, C., Nayak, N., Linda, G. C., Lathi, R. B. ELSEVIER SCIENCE INC. 2010: S47?S47

    View details for Web of Science ID 000281441000162

  • Deep phenotyping to predict live birth outcomes in in vitro fertilization PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Banerjee, P., Choi, B., Shahine, L. K., Jun, S. H., O'leary, K., Lathi, R. B., Westphal, L. M., Wong, W. H., Yao, M. W. 2010; 107 (31): 13570-13575

    Abstract

    Nearly 75% of in vitro fertilization (IVF) treatments do not result in live births and patients are largely guided by a generalized age-based prognostic stratification. We sought to provide personalized and validated prognosis by using available clinical and embryo data from prior, failed treatments to predict live birth probabilities in the subsequent treatment. We generated a boosted tree model, IVFBT, by training it with IVF outcomes data from 1,676 first cycles (C1s) from 2003-2006, followed by external validation with 634 cycles from 2007-2008, respectively. We tested whether this model could predict the probability of having a live birth in the subsequent treatment (C2). By using nondeterministic methods to identify prognostic factors and their relative nonredundant contribution, we generated a prediction model, IVF(BT), that was superior to the age-based control by providing over 1,000-fold improvement to fit new data (p<0.05), and increased discrimination by receiver-operative characteristic analysis (area-under-the-curve, 0.80 vs. 0.68 for C1, 0.68 vs. 0.58 for C2). IVFBT provided predictions that were more accurate for approximately 83% of C1 and approximately 60% of C2 cycles that were out of the range predicted by age. Over half of those patients were reclassified to have higher live birth probabilities. We showed that data from a prior cycle could be used effectively to provide personalized and validated live birth probabilities in a subsequent cycle. Our approach may be replicated and further validated in other IVF clinics.

    View details for DOI 10.1073/pnas.1002296107

    View details for PubMedID 20643955

  • Coexistence of endometriosis in women with symptomatic leiomyomas FERTILITY AND STERILITY Huang, J. Q., Lathi, R. B., Lemyre, M., Rodriguez, H. E., Nezhat, C. H., Nezhat, C. 2010; 94 (2): 720-723

    Abstract

    To investigate the coexistence of endometriosis in women presenting with symptomatic leiomyomas.Retrospective study.Tertiary university medical center.We reviewed the medical records of 131 patients who underwent laparoscopic myomectomy or hysterectomy. All patients were consented for possible concomitant diagnosis and treatment of endometriosis.All patients underwent laparoscopic myomectomy or hysterectomy.The main outcome measure of the study was the presence or absence of endometriosis.Of the 131 patients, 113 were diagnosed with endometriosis and fibroids, while 18 were diagnosed with fibroids alone. Patients with fibroids were on average 4.0 years older than those with endometriosis and fibroids (41 vs. 45). Patients with both diagnoses were also more likely to present with pelvic pain and nulliparity than those with fibroids alone.An overwhelming majority of patients with symptomatic fibroids were also diagnosed with endometriosis. Overlooking the concomitant diagnosis of endometriosis in these women may lead to suboptimal treatment of the patients. Further studies are needed to evaluate the impact of surgical treatments on symptom resolution.

    View details for DOI 10.1016/j.fertnstert.2009.03.052

    View details for Web of Science ID 000279758800047

    View details for PubMedID 19393995

  • Karyotype of miscarriages in relation to maternal weight HUMAN REPRODUCTION Landres, I. V., Milki, A. A., Lathi, R. B. 2010; 25 (5): 1123-1126

    Abstract

    Obesity has been identified as a risk factor for spontaneous miscarriage although the mechanism is unclear. The purpose of this study is to better understand the effect of obesity on early pregnancy success by examining the cytogenetic results of miscarriages in women with normal and elevated body mass index (BMI).We conducted a retrospective case-control study in an academic infertility practice. Medical records of women ages <40 years with first trimester missed abortion (n = 204), who underwent dilatation and curettage between 1999 and 2008, were reviewed for demographics, BMI, diagnosis of polycystic ovary syndrome (PCOS) and karyotype analysis. chi(2) and Student's t-test analysis were used for statistical analysis, with P < 0.05 considered significant.A total of 204 miscarriages were included, from women with a mean age of 34.5 years. The overall rate of aneuploidy was 59%. Women with BMI > or = 25 kg/m(2) had a significant increase in euploid miscarriages compared with women with lower BMI (P = 0.04), despite a similar mean age (34.4 years for both).We found a significant increase in normal embryonic karyotypes in the miscarriages of overweight and obese women (BMI > or = 25). These results suggest that the excess risk of miscarriages in the overweight and obese population is independent of embryonic aneuploidy. Further studies are needed to assess the impact of lifestyle modification, insulin resistance and PCOS on pregnancy outcomes in the overweight and obese population.

    View details for DOI 10.1093/humrep/deq025

    View details for Web of Science ID 000276732800006

    View details for PubMedID 20190263

  • Asian Ethnicity and Poor Outcomes After In Vitro Fertilization Blastocyst Transfer OBSTETRICS AND GYNECOLOGY Langen, E. S., Shahine, L. K., Lamb, J. D., Lathi, R. B., Milki, A. A., Fujimoto, V. Y., Westphal, L. M. 2010; 115 (3): 591-596

    Abstract

    To estimate the effect of ethnicity on in vitro fertilization (IVF) outcomes after blastocyst transfer.We conducted a review of fresh blastocyst transfer IVF cycles from January 1, 2005, to December 31, 2006. Data collection included demographic information, infertility history, treatment protocol details, and treatment outcomes. Statistics were performed using the Student t test and chi2 test. To establish the independent contribution of Asian ethnicity, a multivariable logistic regression analysis was performed.We reviewed 180 blastocyst transfer cycles among white (62%) and Asian (38%) women. The groups were similar in most baseline characteristics. Asian women, however, had a lower body mass index (22.6 compared with 24.2, P=.02), were more likely to be nulligravid (53% compared with 35%, P=.03), and were more likely to have had at least one prior IVF cycle (37% compared with 20%, P=.02) The groups were similar in treatment characteristics, number of oocytes retrieved, fertilization rate, and number of blastocysts transferred. However, Asian women had a thicker endometrial lining (10.9 compared with 10.2, P=.02). Despite these similarities, Asian women had a lower implantation rate (28% compared with 45%, P=.01), clinical pregnancy rate (43% compared with 59%, P=.03), and live birthrate (31% compared with 48%, P=.02). In multivariable analysis, the decreased live birthrate among Asian women persisted (adjusted odds ratio 0.48, 95% confidence interval 0.24-0.96, P=.04).When compared with white women, Asian women have lower clinical pregnancy and live birthrates after blastocyst transfer.

    View details for DOI 10.1097/AOG.0b013e3181cf45c1

    View details for PubMedID 20177291

  • Differential Gene Expression in the Decidua of Recurrent Pregnancy Loss Patients. 57th Annual Meeting of the Society-for-Gynecologic-Investigation Krieg, S. A., Krieg, A. J., Fan, X., Dahl, S., Giaccia, A., Westphal, L. M., Lathi, R., Nayak, N. R. SAGE PUBLICATIONS INC. 2010: 361A?361A

    View details for Web of Science ID 000275558601500

  • Poor Prognosis with In Vitro Fertilization in Indian Women Compared to Caucasian Women Despite Similar Embryo Quality PLOS ONE Shahine, L. K., Lamb, J. D., Lathi, R. B., Milki, A. A., Langen, E., Westphal, L. M. 2009; 4 (10)

    Abstract

    Disease prevalence and response to medical therapy may differ among patients of diverse ethnicities. Poor outcomes with in vitro fertilization (IVF) treatment have been previously shown in Indian women compared to Caucasian women, and some evidence suggests that poor embryo quality may be a cause for the discrepancy. In our center, only patients with the highest quality cleavage stage embryos are considered eligible for extending embryo culture to the blastocyst stage. We compared live birth rates (LBR) between Indian and Caucasian women after blastocyst transfer to investigate whether differences in IVF outcomes between these ethnicities would persist in patients who transferred similar quality embryos.In this retrospective cohort analysis, we compared IVF outcome between 145 Caucasians and 80 Indians who had a blastocyst transfer between January 1, 2005 and June 31, 2007 in our university center. Indians were younger than Caucasians by 2.7 years (34.03 vs. 36.71, P = 0.03), were more likely to have an agonist down regulation protocol (68% vs. 43%, P<0.01), and were more likely to have polycystic ovarian syndrome (PCOS), although not significant, (24% vs. 14%, P = 0.06). Sixty eight percent of Indian patients had the highest quality embryos (4AB blastocyst or better) transferred compared to 71% of the Caucasians (P = 0.2). LBR was significantly lower in the Indians compared to the Caucasians (24% vs. 41%, P<0.01) with an odds ratio of 0.63, (95%CI 0.46-0.86). Controlling for age, stimulation protocol and PCOS showed persistently lower LBR with an adjusted odds ratio of 0.56, (95%CI 0.40-0.79) in the multivariate analysis.Despite younger age and similar embryo quality, Indians had a significantly lower LBR than Caucasians. In this preliminary study, poor prognosis after IVF for Indian ethnicity persisted despite limiting analysis to patients with high quality embryos transferred. Further investigation into explanations for ethnic differences in reproduction is needed.

    View details for DOI 10.1371/journal.pone.0007599

    View details for PubMedID 19855835

  • Effect of selective serotonin reuptake inhibitors on in vitro fertilization outcome 56th Annual Meeting of the Pacific-Coast-Reproductive-Society Friedman, B. E., Rogers, J. L., Shahine, L. K., Westphal, L. M., Lathi, R. B. ELSEVIER SCIENCE INC. 2009: 1312?14

    Abstract

    A review of 950 patients was performed to investigate the impact of selective serotonin reuptake inhibitors (SSRIs) on in vitro fertilization outcome. The 41 patients (4.3%) taking an SSRI had a higher cycle cancellation rate but no statistically significant difference in pregnancy rate and live birth rate per cycle started.

    View details for DOI 10.1016/j.fertnstert.2009.03.060

    View details for Web of Science ID 000270616100027

    View details for PubMedID 19423105

  • Oocyte retrieval versus conversion to intrauterine insemination in patients with poor response to gonadotropin therapy FERTILITY AND STERILITY Shahine, L. K., Lathi, R. B., Baker, V. L. 2009; 92 (4): 1315-1317

    Abstract

    We compared cycle characteristics and outcomes for planned in vitro fertilization cycles with five or fewer developing follicles that proceeded to retrieval (n = 170) with those that converted to intrauterine insemination (IUI) (n = 50). The risk of no embryo transfer was 24% in cycles that proceeded to retrieval. Live birth rate per cycle started was similar for IUI (6%) compared with retrieval (7%).

    View details for DOI 10.1016/j.fertnstert.2009.03.059

    View details for Web of Science ID 000270616100028

    View details for PubMedID 19393998

  • Normal pregnancy after tetraploid karyotype on trophectoderm biopsy FERTILITY AND STERILITY Krieg, S. A., Lathi, R. B., Behr, B., Westphal, L. M. 2009; 92 (3)

    Abstract

    To report a case of successful pregnancy after trophectoderm biopsy and fluorescence in situ hybridization (FISH) revealed a tetraploid karyotype.Case report.A university medical center.An infertility patient desiring trophectoderm biopsy on frozen blastocysts to facilitate preimplantation genetic screening.Frozen blastocysts were thawed on the evening before transfer. Trophectoderm biopsy was performed the following morning. FISH results were available the same day, and two embryos with tetraploid results were transferred.Chorionic villus sample (CVS) and newborn exam.Normal diploid CVS result and a healthy male infant.Although multiple cells can be analyzed using trophectoderm biopsy, abnormalities in the trophectoderm may not be present in the inner cell mass.

    View details for DOI 10.1016/j.fertnstert.2009.06.007

    View details for Web of Science ID 000283282700007

    View details for PubMedID 19608167

  • Effect of methotrexate exposure on subsequent fertility in women undergoing controlled ovarian stimulation 54th Annual Meeting of the Pacific-Coast-Reproductive-Society McLaren, J. F., Burney, R. O., Milki, A. A., Westphal, L. M., Dahan, M. H., Lathi, R. B. ELSEVIER SCIENCE INC. 2009: 515?19

    Abstract

    To evaluate the pregnancy rate, ovarian responsiveness, and endometrial thickness in infertility patients with a history of methotrexate exposure who subsequently underwent controlled ovarian stimulation.Retrospective cohort study.University reproductive endocrinology and infertility program.Forty-eight women with infertility undergoing ovarian stimulation after receiving methotrexate treatment for ectopic gestation.Methotrexate administration and controlled ovarian stimulation.Pregnancy rate, cycle day 3 FSH levels, number of oocytes retrieved, and endometrial thickness.The cumulative intrauterine pregnancy rate achieved with controlled ovarian stimulation at 2 years after methotrexate exposure was 43%, with a mean time to conceive of 181 days. Thirty-five patients with similar fertility treatments pre- and post-methotrexate were identified. Within this group, when an IVF cycle occurred within 180 days of methotrexate exposure, a significant decline in oocytes retrieved was observed. Cycles performed later than 180 days after methotrexate exposure did not exhibit a decrease in oocyte production. Endometrial development was similar at all time points examined.These findings suggest a time-limited and reversible impact of methotrexate on oocyte yield. If confirmed by larger clinical series and/or animal data, these results may impact the management of ectopic gestation in the patient with a history of infertility or the timing of subsequent treatments.

    View details for DOI 10.1016/j.fertnstert.2008.07.009

    View details for PubMedID 18829004

  • Laparoscopy in women with unexplained infertility: a cost-effectiveness analysis FERTILITY AND STERILITY Moayeri, S. E., Lee, H. C., Lathi, R. B., Westphal, L. M., Milki, A. A., Garber, A. M. 2009; 92 (2): 471-480

    Abstract

    To evaluate the cost effectiveness of laparoscopy for unexplained infertility.We performed a cost-effectiveness analysis using a computer-generated decision analysis tree. Data used to construct the mathematical model were extracted from the literature or obtained from our practice. We compared outcomes following four treatment strategies: [1] no treatment, [2] standard infertility treatment algorithm (SITA), [3] laparoscopy with expectant management (LSC/EM), and [4] laparoscopy with infertility therapy (LSC/IT). The incremental cost-effectiveness ratio (ICER) was calculated, and one-way sensitivity analyses assessed the impact of varying base-case estimates.Academic in vitro fertilization practice.Computer-simulated patients assigned to one of four treatments.Fertility treatment or laparoscopy.Incremental cost-effectiveness ratios.Using base-case assumptions, LSC/EM was preferred (ICER =$128,400 per live-birth in U.S. dollars). Changing the following did not alter results: rates and costs of multiple gestations, penalty for high-order multiples, infertility treatment costs, and endometriosis prevalence. Outcomes were most affected by patient dropout from infertility treatments-SITA was preferred when dropout was less than 9% per cycle. Less important factors included surgical costs, acceptability of twins, and the effects of untreated endometriosis on fecundity.Laparoscopy is cost effective in the initial management of young women with infertility, particularly when infertility treatment dropout rates exceed 9% per cycle.

    View details for DOI 10.1016/j.fertnstert.2008.05.074

    View details for PubMedID 18722609

  • Pregnancy after trophectoderm biopsy of frozen-thawed blastocyst FERTILITY AND STERILITY Lathi, R. B., Behr, B. 2009; 91 (5): 1938-1940

    Abstract

    To report a case of a successful pregnancy after trophectoderm biopsy and three-probe fluorescent in situ hybridization of a frozen blastocyst.Techniques and instrumentation.A University Medical Center.Infertility patient desiring trophectoderm biopsy on frozen blastocyst for preimplantation testing, from an IVF cycle at a referring IVF program.Frozen blastocysts were thawed the evening before the planned transfer. Trophectoderm biopsy was performed in the morning. The fluorescent in situ hybridization results were obtained the same day; embryo transfer was performed under ultrasound guidance.Serum betahCG and transvaginal ultrasound.Positive betahCG and ongoing pregnancy.Trophectoderm biopsy can be used as a means for testing frozen blastocysts in patients with excess embryos cryopreserved on day 5 or 6 from previously preformed IVF cycles.

    View details for DOI 10.1016/j.fertnstert.2008.02.132

    View details for Web of Science ID 000265969200055

    View details for PubMedID 18371958

  • Menstrual bleeding from an endometriotic lesion FERTILITY AND STERILITY Burney, R. O., Lathi, R. B. 2009; 91 (5): 1926-1927

    Abstract

    We present a case in which endometriotic lesions were observed to be focally hemorrhagic at laparoscopy performed during menstruation. Red vesicular lesions likely represent early disease with intact capacity for hormonally induced menstrual bleeding.

    View details for DOI 10.1016/j.fertnstert.2008.08.125

    View details for Web of Science ID 000265969200052

    View details for PubMedID 18930191

  • Embryo quality before and after surgical treatment of endometriosis in infertile patients JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Shahine, L. K., Burney, R. O., Behr, B., Milki, A. A., Westphal, L. M., Lathi, R. B. 2009; 26 (2-3): 69-73

    Abstract

    To investigate the hypothesis that surgical treatment of endometriosis in infertile patients may improve pregnancy rates by improving embryo quality.We conducted a retrospective evaluation of 30 infertile patients treated with in vitro fertilization (IVF) before and after surgery for endometriosis. Patients served as their own controls and only cycles with similar stimulation protocols were compared.Using standard visual evaluation, embryo quality on day 3 was similar before and after surgical treatment of endometriosis. Fifty seven percent of patients had stage I-II endometriosis and 43% had stage III-IV disease. No patients had a live birth after the first IVF cycle and 43% of patients had a live birth with the IVF cycle after surgery.Surgical treatment of endometriosis does not alter embryo quality in patients with infertility treated with IVF.

    View details for DOI 10.1007/s10815-008-9287-1

    View details for PubMedID 19214735

  • Basal follicle-stimulating hormone as a predictor of fetal aneuploidy FERTILITY AND STERILITY Massie, J. A., Burney, R. O., Milki, A. A., Westphal, L. M., Lathi, R. B. 2008; 90 (6): 2351-2355

    Abstract

    To determine whether an elevated basal FSH concentration is an independent predictor of fetal aneuploidy, as measured in spontaneous abortions (SAB).Retrospective study.Academic reproductive endocrinology and infertility center.All women with karyotypes of chorionic villi isolated from first trimester spontaneous miscarriages at the time of dilation and curettage from 1999 to 2006. The highest basal serum FSH level in the year preceding dilation and curettage was recorded.Monitoring of early pregnancy.Fetal karyotype.A total of 177 spontaneous miscarriages with karyotypes (70 euploid and 107 aneuploid) were identified, of which 53% were conceived by IVF. The aneuploid cohort consisted of trisomic (87%), teraploid (9.3%), and monosomic (3.7%) gestations. Using logistic regression analysis, basal FSH was not found to be independently predictive of an aneuploid gestation in our data set.Our data do not support the hypothesis that an elevated basal FSH concentration is associated with an increase in fetal aneuploidy. Our findings suggest that the association between diminished ovarian reserve and SAB may result from nonkaryotypic factors.

    View details for DOI 10.1016/j.fertnstert.2007.10.041

    View details for PubMedID 18178189

  • Transvaginal ligation of the cervical branches of the uterine artery and injection of vasopressin initial in a cervical pregnancy as an step to controlling hemorrhage - A case report JOURNAL OF REPRODUCTIVE MEDICINE Davis, L. B., Lathi, R. B., Milki, A. A., Dahan, M. H. 2008; 53 (5): 365-368

    Abstract

    Hemorrhage from a cervical pregnancy is a time-sensitive matter. Effective temporization measures for the initial management of this hemorrhage have not previously been reported in the literature.A 43-year-old woman, gravida 0, underwent in vitro fertilization and embryo transfer. She subsequently presented to the office with sudden onset of vaginal hemorrhage due to a cervical pregnancy. Cervical artery sutures were placed, and a cervical vasoconstricting agent was injected, at which point the patient's bleeding stopped. She then underwent successful treatment with dilation and curettage.Conservative measures to manage hemorrhage due to cervical pregnancy can be initiated, with possible rapid establishment of hemostasis until definitive treatment can be achieved.

    View details for PubMedID 18567285

  • The effect of selective serotonin reuptake inhibitors on in vitro fertilization outcome 56th Annual Meeting of the Pacific-Coast-Reproductive-Society Friedman, B. E., Rogers, J. L., Shahine, L. K., Westphal, L. M., Lathi, R. B. ELSEVIER SCIENCE INC. 2008: S12?S12

    View details for Web of Science ID 000255250200021

  • Diagnosis of stage I endometriosis: Comparing visual inspection to histologic biopsy specimen 35th Annual Meeting of the American-Association-of-Gynecologic-Laparoscopists Kazanegra, R., Zaritsky, E., Lathi, R. B., Clopton, P., Nezhat, C. ELSEVIER SCIENCE INC. 2008: 176?80

    Abstract

    To evaluate positive predictive value (PPV) of visual diagnosis at laparoscopy compared with biopsy findings according to severity of endometriosis.Retrospective study (Canadian Task Force classification II-2).Academic referral center.Women who underwent laparoscopic biopsies for suspected endometriosis.A total of 238 biopsy specimens (73 endometriomas and 165 peritoneal implants) were taken from 104 patients undergoing laparoscopy for evaluation of chronic pelvic pain thought to be caused by endometriosis.Accuracy of laparoscopic findings compared with histology-proved endometriosis by severity of disease and location of endometriotic lesions. Overall PPV per patient was 86.5%, which was 75.8% for stage I disease compared with 89.7%, 100%, and 90.6%, respectively, for disease stages II to IV (p = .037). The PPV per biopsy specimen of stages I to IV endometriosis was 66.1%, 78.0%, 92.0%, and 81.1%, respectively (.049). When endometriomas and peritoneal biopsy specimens were analyzed separately, no difference in PPV existed (79% vs 77%; p = .67).High overall PPV existed in our study, especially in patients with advanced disease. The PPV per patient was higher than the PPV per biopsy specimen indicating that ability to diagnose endometriosis may be improved by performing multiple biopsies. This is particularly true in stage I where failure to confirm may be greatest.

    View details for DOI 10.1016/j.jmig.2007.10.005

    View details for Web of Science ID 000253965000009

    View details for PubMedID 18312987

  • Aneuploidy in the miscarriages of infertile women and the potential benefit of preimplanation genetic diagnosis FERTILITY AND STERILITY Lathi, R. B., Westphal, L. M., Milki, A. A. 2008; 89 (2): 353-357

    Abstract

    To evaluate the frequency of specific aneuploidies in miscarriages in an infertility practice and calculate the potential sensitivities of the different aneuploidy screening options for preimplantation genetic diagnosis (PGD) in this setting.Retrospective analysis.Academic reproductive endocrinology and infertility practice.Women with miscarriages that had karyotype analysis on products of conception.None.Karyotype of spontaneous abortions compared with commercially available PGD options.Of the 273 karyotypes analyzed, 177 (64.8%) were abnormal. The average age of the patients was 37 +/- 4.5 years. Using a limited five-probe panel, 54 of the 177 (31%) abnormal karyotypes would have been detected. In contrast, an extended PGD panel (using 9, 10, or 12 chromosome probes) would have detected 127, 131, and 140 of 177 abnormalities, 72%, 74%, and 79% respectively. The difference between the limited (5-probe) and extended (9-, 10-, and 12-probe) panels was statistically significant. There was not a statistically significant difference among the extended panels.Most of the abnormalities seen in miscarriages are detectable by PGD with extended panels. A significantly higher percentage of these abnormalities could be detected by screening for 9, 10, or 12 chromosomes compared with only 5.

    View details for DOI 10.1016/j.fertnstert.2007.02.040

    View details for PubMedID 17509575

  • Elective single blastocyst transfer in women older than 35 FERTILITY AND STERILITY Davis, L. B., Lathi, R. B., Westphal, L. M., Milki, A. A. 2008; 89 (1): 230-231

    Abstract

    A retrospective review of all patients older than 35 who underwent elective single blastocyst transfer was performed. Twenty-three of the 45 patients (51.1%) have an ongoing pregnancy or liveborn delivery, with a mean age of 37.3 years, demonstrating a clear role for elective single transfer in this relatively older IVF population.

    View details for DOI 10.1016/j.fertnstert.2007.02.047

    View details for PubMedID 17509586

  • Cytogenetic testing of anembryonic pregnancies compared to embryonic missed abortions JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Lathi, R. B., Mark, S. D., Westphal, L. M., Milki, A. A. 2007; 24 (11): 521-524

    Abstract

    The objective of this study is to determine the rate of abnormalities detected by cytogenetic testing of first trimester miscarriages, in patients with and without an embryonic pole seen on ultrasound.A retrospective study of 272 D&Cs for missed abortions in an academic infertility practice from 1999 to 2006. Karyotype results were compared with transvaginal ultrasound findings. Chi-squared analysis was used with a P < 0.05 for significance.There was a high rate of abnormal karyotypes in all miscarriages (65%). Rates of abnormal karyotypes were 58% and 68% in cases with anembryonic gestations and those with a fetal pole seen, respectively (P > 0.05).The high rate of abnormalities detected in both groups suggests that useful results can be obtained from chromosomal testing of the POC regardless of ultrasound findings. Further studies on the prognostic value and cost effectiveness of chromosomal testing are needed.

    View details for DOI 10.1007/s10815-007-9166-1

    View details for PubMedID 17899357

  • Preoperative vaginal preparation with baby shampoo compared with povidone-iodine before gynecologic procedures JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY Lewis, L. A., Lathi, R. B., Crochet, P., Nezhat, C. 2007; 14 (6): 736-739

    Abstract

    The objective of this study was to compare the postoperative infection rates between patients receiving either povidone-iodine (PI) or baby shampoo vaginal preparations before gynecologic surgery.Cohort study (Canadian Task Force classification II-2).University referral center for gynecologic endoscopy.All patients underwent minimally invasive gynecologic surgery including hysteroscopy or laparoscopy.The agents used for vaginal preparation were either baby shampoo in a 1:1 dilution with sterile normal saline solution or PI 7.5% scrub solution.Charts were reviewed for evidence of infection within 30 days of surgery (symptoms of urinary tract infection, abdominal or vaginal wound infections, temperature > 100.4 degrees F, and fungal or bacterial vaginitis). A total of 249 cases were collected; 96 subjects underwent surgery before the change to baby shampoo and 153 subjects after. Both groups were well matched for the types of surgery performed, age, risk factors for postoperative infections, and the postoperative diagnosis. The infection rates were 14/96 (14.6%) with PI preparation versus 18/153 (11.8%) with baby shampoo (p = .52).Baby shampoo should be studied as an alternative to PI because it is a nonirritating, inexpensive mild detergent. This preliminary study suggests that baby shampoo is as effective as PI in preventing postoperative infection.

    View details for DOI 10.1016/j.jmig.2007.05.010

    View details for Web of Science ID 000250986900013

    View details for PubMedID 17980335

  • Pelvic pain after gonadotropin administration as a potential sign of endometriosis FERTILITY AND STERILITY Jun, S. H., Lathi, R. B. 2007; 88 (4): 986-987

    Abstract

    We describe five patients who developed significant pelvic pain, requiring narcotics, during a controlled ovarian hyperstimulation cycle and who were surgically diagnosed with significant endometriosis. Severe pain, especially if it requires narcotics, is unusual for patients undergoing controlled ovarian hyperstimulation and may be an indicator of endometriosis.

    View details for DOI 10.1016/j.fertnstert.2006.12.054

    View details for Web of Science ID 000250192800034

    View details for PubMedID 17428478

  • A comparison of letrozole to gonadotropins for ovulation induction, in subjects who failed to conceive with clomiphene citrate WRHR Scholars Symposium Quintero, R. B., Urban, R., Lathi, R. B., Westphal, L. M., Dahan, M. H. ELSEVIER SCIENCE INC. 2007: 879?85

    Abstract

    To compare pregnancy rates (PR) for letrozole and gonadotropins in individuals who failed to conceive with clomiphene citrate (CC).Retrospective cohort study.University reproductive center.Individuals treated with letrozole or gonadotropins who failed to conceive with CC.Controlled ovarian hyperstimulation (COH), transvaginal ultrasound, ovulation induction, IUI.Pregnancy rates per cycle.Among patients who failed to conceive with at least three cycles of CC, gonadotropins had a higher PR per cycle than letrozole. Among individuals who failed to conceive with less than three cycles of CC and whose medications were changed because of thin uterine lining or intolerable side effects, average PR per cycle for letrozole and gonadotropin treatments were equivalent. All patients conceived within three stimulation cycles with either gonadotropins or letrozole.In patients who failed to conceive with CC, gonadotropins have higher PR for ovulation induction than letrozole. However, PR were high enough with letrozole to justify its use in this population of patients. Letrozole and gonadotropins should not be used for more than three cycles without a conception.

    View details for DOI 10.1016/j.fertnstert.2006.11.166

    View details for PubMedID 17920403

  • The effect of infertility medication on thyroid function in hypothyroid women who conceive THYROID Davis, L. B., Lathi, R. B., Dahan, M. H. 2007; 17 (8): 773-777

    Abstract

    To determine whether infertility medications alter thyroid status in patients with treated hypothyroidism, and whether resulting pregnancies require additional thyroid supplementation compared with those conceived spontaneously.Prospective observational study of 18 infertility patients with treated hypothyroidism who conceived between July 2005 and July 2006 with or without infertility medications. Thyroid studies were performed prior to conception, at the time of pregnancy diagnosis, and approximately 6 weeks after an increase in thyroid replacement dose.Orally medicated conceptions were similar to spontaneous conceptions on all thyroid related variables, and therefore the two groups were combined for analysis. Although there was a nonsignificant difference in thyrotropin (TSH) levels postconception (3.8 mIU/L vs. 2.2 mIU/L, p = 0.30), there was no difference in TSH levels after increase in thyroid replacement dose (1.7 mIU/L vs. 1.1 mIU/L, p = 0.30) between patients who conceived after gonadotropin stimulation compared with those who conceived spontaneously or with oral medications. The mean percent dose increases for the nongonadotropin and gonadotropin pregnancy groups were 30.6% and 32.4%, respectively.Hypothyroid patients who conceive after gonadotropin stimulation or with oral medications for ovulation induction do not need additional thyroid supplementation compared with those who conceive spontaneously.

    View details for DOI 10.1089/thy.2007.0065

    View details for Web of Science ID 000249145300011

    View details for PubMedID 17725435

  • Rupture of ectopic pregnancy with minimally detectable beta-human chorionic gonadotropin levels: A report of 2 cases JOURNAL OF REPRODUCTIVE MEDICINE Fu, J., Henne, M. B., Blumstein, S., Lathi, R. B. 2007; 52 (6): 541-542

    Abstract

    Several studies have demonstrated that 25-77% of ectopic pregnancies spontaneously resolve with expectant management. However, expectant management is controversial and should be considered only for patients with small, unruptured gestational sacs, low beta-human chorionic gonadotropin (beta-hCG) levels and absence of symptoms. There is no consensus on how long to follow such patients.Two patients with beta-hCG levels < 10 mIU/mL presented with ruptured ectopic pregnancy and hemoperitoneum.While expectant management of a suspected ectopic pregnancy may allow spontaneous resolution of such an ectopic pregnancy, rupture may occur at any time and even with extremely low beta-hCG levels. Patients need to be counseled about the risks of rupture and symptoms, immediate action should be taken if symptoms develop, and serum beta-hCG levels should be followed to zero.

    View details for Web of Science ID 000247354600017

    View details for PubMedID 17694977

  • Metformin and fetal malformations FERTILITY AND STERILITY Shahine, L., Lathi, R. B., Dahan, M. H. 2007; 87 (5): 1240-1240

    View details for DOI 10.1016/j.fertnstert.2007.03.021

    View details for Web of Science ID 000246583600037

    View details for PubMedID 17400214

  • Risk of monozygotic twinning with blastocyst transfer decreases over time: an 8-year experience FERTILITY AND STERILITY Moayeri, S. E., Behr, B., Lathi, R. B., Westphal, L. M., Milki, A. A. 2007; 87 (5): 1028-1032

    Abstract

    The purpose of our study is to compare the occurrence of monozygotic twinning (MZT) from blastocyst transfer (BT) in our program between an earlier and more recent time period.Retrospective.Academic IVF practice.All pregnancies conceived between March 2002 and December 2005 (N = 932) in our program were compared to pregnancies conceived before March 2002 (N = 554), which were the subject of a previous study.None.The incidence of MZT with day 3 embryo transfer and BT were compared between the study and control groups.During the study period, the rate of MZT was not significantly different for BT at 2.3% (9/385) compared to day 3 embryo transfer at 1.8% (10/547). This rate of 2.3% for BT was significantly lower than the rate of 5.6% (11/197) reported at our institution for BT before March 2002.Our study suggests that the risk of MZT with BT is significantly lower in the more recent time period and is in the range of what is seen with cleavage stage transfer. It is likely that improvements in culture systems as experience is gained with BT played a role.

    View details for DOI 10.1016/j.fertnstert.2006.09.013

    View details for PubMedID 17343858

  • Serum total testosterone levels in a patient with late onset 21-hydroxylase deficiency and a twin gestation FERTILITY AND STERILITY Mains, L. M., Lathi, R. B., Burney, R. O., Dahan, M. H. 2007; 87 (5)

    Abstract

    To present serum androgen levels during pregnancy in a twin gestation complicated by maternal late onset 21-hydroxylase deficiency.Case report.University teaching hospital reproductive endocrinology and infertility practice.A 27-year-old with nonclassic 21-hydroxylase deficiency and infertility, twin female fetuses, and elevated androgens.Steroid replacement.Serum T and 17-hydroxyprogesterone (17-OHP) levels.Elevated androgen levels persisted throughout pregnancy in spite of aggressive steroid replacement. However, twin girls were born without any evidence of virilization.The changes associated with a twin gestation may result in excessive stimulation of androgens in mothers with nonclassic 21-hydroxylase deficiency. However, the increased placental aromatase provides protection.

    View details for DOI 10.1016/j.fertnstert.2006.07.1545

    View details for Web of Science ID 000207688100002

    View details for PubMedID 17418835

  • Effect of reduced oxygen concentrations on the outcome of in vitro fertilization FERTILITY AND STERILITY Kea, B., Gebhardt, J., Watt, J., Westphal, L. M., Lathi, R. B., Milki, A. A., Behr, B. 2007; 87 (1): 213-216

    Abstract

    We compared the effects of two standard oxygen concentrations, physiological (5% O(2), 5% CO(2), and 90% N(2)) and atmospheric (5% CO(2) with the balance as air), on fertilization, embryo development, and pregnancy rate in 106 patients undergoing IVF, excluding donor oocyte cycles and preimplantation genetic diagnosis cycles. The differences in oxygen concentration did not significantly affect fertilization rate, blastocyst formation, or pregnancy rate, but there was a significant difference in mean embryo score between physiological and atmospheric groups on day 3.

    View details for DOI 10.1016/j.fertnstert.2006.05.066

    View details for PubMedID 17081523

  • Night sweats and elevated follicle-stimulating hormone levels while taking selective serotonin reuptake inhibitors OBSTETRICS AND GYNECOLOGY Shahine, L. K., Lathi, R. B. 2006; 108 (3): 741-742

    Abstract

    Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to women with depression and anxiety disorders. Although night sweats are a reported adverse effect, some women have relief of vasomotor symptoms during perimenopausal period while taking them. The relationships between SSRIs, thermoregulation, gonadotropins, and estrogen and their connection to fertility remain unclear.A reproductive-aged woman, seeking treatment for infertility, experienced night sweats and elevated follicle-stimulating hormone levels while taking SSRIs for treatment of depression.Many women of reproductive age are taking SSRIs, but the affect of SSRIs on normal reproductive function is unknown and further research in this area is needed.

    View details for Web of Science ID 000247038500016

    View details for PubMedID 17018486

  • Optimal ovarian stimulation protocol for IVF-ET treatment in the patient with endometriosis. 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM) Burney, R. O., Henne, M., Jacobson, M. T., Milki, A. A., Westphal, L. M., Lathi, R. B. ELSEVIER SCIENCE INC. 2006: S275?S275

    View details for Web of Science ID 000241038501145

  • Congenital interruption of the ampullary portion of the fallopian tube FERTILITY AND STERILITY Dahan, M. H., Burney, R., Lathi, R. 2006; 85 (6): 1820-1821

    Abstract

    We present a rare case of a congenital isolated missing segment of the fallopian tube, including hysterosalpingographic and laparoscopic images. We conclude that when this occurs without concomitant müllerian anomalies, the mechanism of development would not be expected to be associated with an increase in renal abnormalities.

    View details for DOI 10.1016/j.fertnstert.2006.01.012

    View details for Web of Science ID 000238427700031

    View details for PubMedID 16678820

  • Predictive value of magnetic resonance imaging in differentiating between leiomyoma and adenomyosis. JSLS : Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons Moghadam, R., Lathi, R. B., Shahmohamady, B., Saberi, N. S., Nezhat, C. H., Nezhat, F., Nezhat, C. 2006; 10 (2): 216-219

    Abstract

    We evaluated the role of MRI as a preoperative diagnostic tool for leiomyoma and adenomyosis.This is a retrospective chart review at a university-based hospital. The study included 1517 women who underwent hysterectomy or myomectomy over a 5-year period, and 153 women with a preoperative pelvic MRI were included. Comparisons were made between the results of the MRI and postoperative pathology reports.The MRI and pathology report were the same for 136 of 144 women with leiomyoma and 12 of 31 women with adenomyosis. The MRI had 94% sensitivity and 33% specificity for leiomyoma and 38% sensitivity and 91% specificity for adenomyosis. Positive and negative predictive values of MRI for leiomyoma were 95% and 27% with 90% accuracy. Positive and negative predictive values of MRI for adenomyosis were 52% and 85%, respectively, with 80% accuracy.MRI has a high sensitivity and a low specificity for diagnosing leiomyoma and a high specificity and a low sensitivity for diagnosing adenomyosis. Due to the high cost and technical variations, we suggest using MRI only as an adjunctive diagnostic tool when ultrasound is not conclusive and differentiation between the 2 pathologies ultimately affects patient management.

    View details for PubMedID 16882423

  • Comparison of letrozole to gonadotropins (FSH) for ovulation induction in clomiphene (CC) failures. 54th Annual Meeting of the Pacific-Coast-Reproductive-Society Wen, Y., Quintero, R. B., Urban, R., Westphal, L. M., Lathi, R. B., Dahan, M. H. ELSEVIER SCIENCE INC. 2006: S24?S25

    View details for Web of Science ID 000236902400056

  • Role of laparoscopic treatment of endometriosis in patients with failed in vitro fertilization cycles FERTILITY AND STERILITY Littman, E., Giudice, L., Lathi, R., Berker, B., Milki, A., Nezhat, C. 2005; 84 (6): 1574-1578

    Abstract

    To report our experience in patients with previous IVF failures who conceived after laparoscopic treatment of endometriosis.Retrospective case series.Tertiary center IVF and endoscopy programs.Infertility patients with history of prior IVF failures.Laparoscopic evaluation and treatment of endometriosis by the same surgeon.Occurrence of conception after laparoscopic treatment of endometriosis.Of 29 patients with prior IVF failures, 22 conceived after laparoscopic treatment of endometriosis, including 15 non-IVF pregnancies and 7 IVF pregnancies.In the absence of tubal occlusion or severe male factor infertility, laparoscopy may still be considered for the treatment of endometriosis even after multiple IVF failures.

    View details for DOI 10.1016/j.fertnstert.2005.02.059

    View details for PubMedID 16359945

  • The dilemma of endometriosis: is consensus possible with an enigma? FERTILITY AND STERILITY Nezhat, C., Littman, E. D., Lathi, R. B., Berker, B., Westphal, L. M., Giudice, L. C., Milki, A. A. 2005; 84 (6): 1587-1588

    Abstract

    Many will agree that the use of laparoscopy to diagnose and potientially treat endometriosis in patients who suffer from infertility has been superseded by IVF and sometimes oocyte donation, especially in older patients. The findings of our study add another dimension to management of endometriosis in the setting of infertility and emphasize the importance of keeping laparoscopy in the infertility management equation.

    View details for DOI 10.1016/j.fertnstert.2005.06.033

    View details for PubMedID 16359950

  • Ruptured ectopic pregnancy with minimally detectable Beta-HCG level. 53rd Annual Meeting of the Pacific-Coast-Reproductive-Society Fu, J., Henne, M. B., Blumstein, S. L., Lathi, R. B. ELSEVIER SCIENCE INC. 2005: S25?S26

    View details for Web of Science ID 000229048000055

  • Dose-dependent insulin regulation of insulin-like growth factor binding protein-1 in human endometrial stromal cells is mediated by distinct signaling pathways JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Lathi, R. B., Hess, A. P., Tulac, S., Nayak, N. R., Conti, M., Giudice, L. C. 2005; 90 (3): 1599-1606

    Abstract

    IGF binding protein-1 (IGFBP-1) is a major product of decidualized human endometrial stromal cells and decidua, and as a modulator of IGF action and/or by independent mechanisms, it regulates cell growth and differentiation and embryonic implantation in these tissues. IGFBP-1 secretion is primarily stimulated by progesterone and cAMP and is inhibited by insulin and IGFs. The signaling pathways mediating the latter are not well defined, and the current study was conducted to determine which pathways mediate the effects of insulin on IGFBP-1 mRNA and protein expression by human endometrial stromal cells decidualized in vitro by progesterone. Cells were cultured and treated with different combinations of insulin; wortmannin, an inhibitor of the phosphatidylinositide-3-kinase (PI3-kinase) pathway; and PD98059, an inhibitor of the MAPK pathway. IGFBP-1 mRNA was determined by real-time PCR, and protein secretion in the conditioned medium was measured by ELISA. Activation of the PI3-kinase and the MAPK pathways was assessed by the detection of phosphorylated AKT and ERK in Western blots, respectively. Insulin inhibited IGFBP-1 mRNA and protein secretion in a dose-dependent fashion, with an ED(50) for the latter 0.127 ng/ml (21.6 pm). Inhibitor studies revealed that at low doses, insulin acts through the PI3-kinase pathway, whereas at higher levels it also activates the MAPK pathway in the inhibition of IGFBP-1. The data demonstrate that human endometrium is a target for insulin action in the regulation of IGFBP-1. At physiological levels insulin likely plays a homeostatic role for energy metabolism in the endometrium, and in hyperinsulinemic states, insulin action on the endometrium may activate cellular mitosis via the MAPK pathway and perhaps predispose this tissue to hyperplasia and/or cancer.

    View details for DOI 10.1210/jc.2004-1676

    View details for Web of Science ID 000227523600050

    View details for PubMedID 15613433

  • Rate of aneuploidy in miscarriages following in vitro fertilization and intracytoplasmic sperm injection FERTILITY AND STERILITY Lathi, R. B., Milki, A. A. 2004; 81 (5): 1270-1272

    Abstract

    To evaluate the incidence of aneuploidy in miscarriages after IVF and intracytoplasmic sperm injection (ICSI) procedures.Retrospective study.University IVF program.All IVF patients with missed abortions undergoing uterine curettage.Cytogenetic analysis of products of conception (POC).Incidence of aneuploidy in POC.Thirty-two of 59 specimens (54%) reviewed were abnormal. The patients with ICSI were more likely to have aneuploidy identified in their POC than conventional IVF, 76% vs. 41%. The average ages in these groups were similar: 37.1 vs. 37.8 years. There was a trend toward decreased aneuploidy with day 5 compared to day 3 embryo transfers; 38% vs. 63%.We found a significantly higher aneuploidy rate in the abortuses of patients who conceived with ICSI. It is possible that this increased incidence is due to abnormalities in the sperm of patients with ICSI, but could also be partially related to the technique itself.

    View details for DOI 10.1016/j.fertnstert.2003.09.065

    View details for PubMedID 15136088

  • Interferon-related and other immune genes are downregulated in peripheral blood leukocytes in the luteal phase of the menstrual cycle JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Dosiou, C., Lathi, R. B., Tulac, S., Huang, S. T., Giudice, L. C. 2004; 89 (5): 2501-2504

    Abstract

    Interaction between the endocrine and the immune systems has been suggested by observations of sexual dimorphism of the immune response, differential susceptibility to autoimmunity between the sexes, changes in autoimmune disease activity during the menstrual cycle and in pregnancy and in vitro studies of hormonal influence on cytokine production.We hypothesized that if there is hormonal regulation of the immune response, this would be manifest in peripheral blood leukocytes (PBLs) at different phases of the menstrual cycle. In this study, we describe gene profiling of PBLs from the follicular and luteal phases of the menstrual cycle. We observe important differences in immune gene expression, with significant down-regulation of the Th1 immune response in the luteal phase. A significant number of interferon (IFN)-related genes are amongst the downregulated genes. These results support significant hormonal regulation of the immune system and may have therapeutic implications in diseases of autoimmunity in women.

    View details for DOI 10.1210/jc.2003-031647

    View details for Web of Science ID 000221220100076

    View details for PubMedID 15126584

  • Tissue sampling technique affects accuracy of karyotype from missed abortions JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Lathi, R. B., Milki, A. A. 2002; 19 (11): 536-538

    Abstract

    To determine if careful specimen selection and washing of tissue from first trimester missed abortion products of conception specimens increases the sensitivity of routine cytogenetics in detecting aneuploidy.Retrospective review of cytogenetics results from tissue from dilation and curettage for missed abortion in a university fertility practice between 1998 and 2001. A technique of careful selection and washing of the specimen was implemented in July 1999. Results from before (n = 15) and after (n = 41) this change were compared. Cytogenetics reports from other physicians using the same laboratory were used for comparison (n = 59).The percentage of 46XX results was significantly decreased in the test group when compared to historical and community controls: 29% vs. 73% and 56% respectively. The percentage of aneuploid results was significantly higher in the test group at 61% vs. 7% and 36% in the historical and community controls respectively.Thorough separation and cleaning of villi prior to sending missed abortion specimens significantly increases sensitivity of conventional cytogenetics for detecting aneuploidy by decreasing maternal contamination.

    View details for PubMedID 12484496

  • Changes in cytokine expression in peripheral leukocytes, detected by microarray analysis, in the secretory vs proliferative phase of the menstrual cycle. 58th Annual Meeting of the American-Society-for-Reproductive-Medicine Lathi, R. B., Tulac, S., Lobo, S. C., Huang, S. T., Giudice, L. C. ELSEVIER SCIENCE INC. 2002: S109?S109

    View details for Web of Science ID 000178239400287

  • Recombinant gonadotropins. Current women's health reports Lathi, R. B., Milki, A. A. 2001; 1 (2): 157-163

    Abstract

    Recombinant DNA technology makes it possible to produce large amounts of human gene products for pharmacologic applications, supplanting the need for human tissues. The genes for the alpha and beta subunits of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG) have been characterized and cloned. Recombinant FSH (rFSH) has been shown to be safe and effective in the treatment of fertility disorders. In comparison with the urinary gonadotropin products, human menopausal gonadotropins (HMG), and urinary follitropins (uFSH), rFSH is more potent and better tolerated by patients. Recombinant HCG appears to be as efficacious as urinary HCG with the benefit of improved local tolerance. Recombinant LH (rLH) is likely to be recommended as a supplement to rFSH for ovulation induction in hypogonadotropic women. It may also benefit in vitro fertilization patients undergoing controlled ovarian hyperstimulation with rFSH combined with pituitary suppression, with a gonadotropin-releasing hormone agonist or antagonist.

    View details for PubMedID 12112963

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