Publications

Director of Research, Stanford, Reproductive Endocrinology and Infertility (2020 - Present) Director, Recurrent Pregnancy Loss Program, Reproductive Endocrinology & Infertilty Division, Stanford University (2007 - Present) 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)

Publications

  • 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

  • Association between preconception paternal health and pregnancy loss in the USA: an analysis of US claims data. Human reproduction (Oxford, England) Kasman, A. M., Zhang, C. A., Li, S. n., Lu, Y. n., Lathi, R. B., Stevenson, D. K., Shaw, G. M., Eisenberg, M. L. 2020

    Abstract

    Is preconception paternal health associated with pregnancy loss?Poor preconception paternal health is associated with a higher risk of pregnancy loss as confirmed in sensitivity analyses accounting for maternal age and health.Preconception paternal health can negatively impact perinatal outcomes.Retrospective cohort study of US insurance claims database from 2009 to 2016 covering 958 804 pregnancies.US insurance claims database including women, men and pregnancies within the USA between 2007 and 2016. Paternal preconception health status (e.g. metabolic syndrome diagnoses (MetS), Charlson comorbidity index (CCI) and individual chronic disease diagnoses) was examined in relation to pregnancy loss (e.g. ectopic pregnancy, miscarriage and stillbirth).In all, 958 804 pregnancies were analyzed. The average paternal age was 35.3 years (SD 5.3) and maternal age was 33.1 years (SD 4.4). Twenty-two percent of all pregnancies ended in a loss. After adjusting for maternal factors, the risk of pregnancy loss increased with increasing paternal comorbidity. For example, compared to men with no components of MetS, the risk of pregnancy loss increased for men with one (relative risk (RR) 1.10, 95% CI 1.09-1.12), two (RR 1.15, 95% CI 1.13-1.17) or three or more (RR 1.19, 95% CI 1.14-1.24) components. Specifically, less healthy men had a higher risk of siring a pregnancy ending in spontaneous abortion, stillbirth and ectopic pregnancies. Similar patterns remained with other measures of paternal health (e.g. CCI, chronic diseases, etc.). When stratifying by maternal age as well as maternal health, a similar pattern of increasing pregnancy loss risk for men with 1, 2 or 3+ MetS was observed. A statistically significant but weak association between timing of pregnancy loss and paternal health was found.Retrospective study design covering only employer insured individuals may limit generalizability.Optimization of a father's health may improve pregnancy outcomes.National Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award (UL1 TR001085). M.L.E. is an advisor for Sandstone Diagnostics, Dadi, Hannah and Underdog. No other competing interests were declared.N/A.

    View details for DOI 10.1093/humrep/deaa332

    View details for PubMedID 33336240

  • 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
  • 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
  • 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

  • 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

  • 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

  • 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
  • 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

  • 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