Emeritus Faculty, Acad Council, Obstetrics & Gynecology
To examine the relationship of ovulation-inducing drugs and ovarian cancer.Retrospective cohort study, with additional follow-up since initial report.Five large reproductive endocrinology practices.In a retrospective cohort of 9,825 women evaluated for infertility at five clinical sites in the United States between 1965 and 1988 with follow-up through 2010, we examined the relationship of ovulation-inducing drugs and ovarian cancer (n = 85).None.Hazard rate ratios (RR) and 95% confidence intervals (CI) for ovarian cancer.Among women evaluated for infertility, there was no association of ovarian cancer risk with ever use of clomiphene citrate (CC) (adjusted RR 1.34, 95% CI 0.86-2.07) or gonadotropins (RR 1.00, 95% CI 0.48-2.08) and no evidence that any of several more detailed subgroups of usage were related to an increased risk with one exception: women who used CC and remained nulligravid did demonstrate much higher risks than those who successfully conceived compared with nonusers (respectively, RR 3.63, 95% CI 1.36-9.72 vs. RR 0.88, 95% CI 0.47-1.63).Our overall results were reassuring and consistent with other studies. A reason for an association between CC use and ovarian cancer among persistently nulligravid women remains to be determined. Given the large and increasing number of women treated with ovulation-inducing drugs, the increased risk of ovarian cancer among the subset of women who remained nulligravid should be further monitored.
View details for DOI 10.1016/j.fertnstert.2013.08.008
View details for Web of Science ID 000327533000036
View details for PubMedID 24011610
Do fertility drugs influence the subsequent risk of endometrial cancer in a manner that is independent of other risk predictors, such as parity?In this follow-up of a large cohort of women evaluated for infertility and for whom information was captured on fertility drugs, indications for usage and other risk factors that might influence cancer risk, we found no evidence for a substantial relationship between fertility drug use and endometrial cancer risk.Although the hormonal etiology of endometrial cancer has been well established, it remains unclear whether the use of fertility drugs has an influence on risk. Results regarding the effects of fertility drugs on endometrial cancer risk have been inconsistent, although several studies have shown some evidence for possible increases in risk. The relationship is of particular interest given that clomiphene, a commonly prescribed drug, is a selective estrogen receptor modulator, with chemical properties similar to tamoxifen, another drug linked to an increase in endometrial cancer risk.In a retrospective cohort of 12 193 women evaluated for infertility between 1965 and 1988 at five US sites, follow-up was pursued through 2010 via both passive as well as active (questionnaire) means.Among the 9832 subjects for whom follow-up was allowed and achieved, 259 346 at-risk person-years (i.e. prior to hysterectomy) were accrued, and 118 invasive endometrial cancers identified. Cox regression determined hazard ratios (HRs) and 95% confidence intervals (CIs) for fertility treatments adjusted for endometrial cancer risk factors and causes of infertility.Although we observed slight increases in endometrial cancer risk associated with clomiphene (HR = 1.39, 95% CI: 0.96-2.01) and the less commonly prescribed gonadotrophins (1.34, 0.76-2.37), there were no convincing relationships of risk with either cycles of use or cumulative exposures for either drug. A statistically significant risk associated with the use of clomiphene among women who began use at younger ages (<30) (1.93, 1.24-3.00) may have reflected indications for drug usage rather than the effect of the drug itself. Women who received clomiphene followed by gonadotrophins were at a non-significantly elevated risk (1.77, 0.98-3.19).Like most studies of endometrial cancer, we were limited by sample sizes, particularly for evaluating subgroup associations. We were also unable to follow all women and were not able to obtain complete risk factor information (including hysterectomy status) for the entire cohort.Although we found no support for a relationship between fertility drugs and endometrial cancer risk, the association should continue to be monitored given that our study population was still young and had not yet reached the age of peak endometrial cancer incidence.This project was supported in part by funds from the intramural research program of the National Cancer Institute, National Institutes of Health. None of the authors has any conflicting interests to declare.
View details for DOI 10.1093/humrep/det323
View details for Web of Science ID 000324836300024
View details for PubMedID 23943795
To define relationships of androgen excesses to cancer risk.Retrospective cohort study.Five large infertility practices.Among 12,193 women evaluated for infertility during 1965-1988 and traced for cancer incidence through 1999, 2,560 had androgen excess or menstrual disorders; among these, 412 met established criteria for polycystic ovary syndrome.None.Cancer incidence. Derivation of standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for cancer risk comparisons with the general population and rate ratios (RRs) for comparisons with other infertility patients.Androgen excess/menstrual disorder patients showed significant SIRs for breast (1.31; 95% CI, 1.05-1.62) and uterine (2.02; 95% CI, 1.13-3.34) cancers and melanoma (1.96; 95% CI, 1.12-3.18). Significant associations for breast and uterine cancers were restricted to primary infertility patients (respective SIRs of 1.53 and 3.48). After adjustment for other cancer predictors, the only excess risk was for uterine cancer among primary infertility patients. Compared with women with secondary infertility and no androgen excess/menstrual disorder, those with primary infertility and a disorder had an RR of 1.88 (95% CI, 0.82-4.32). Cancer risks among the women with polycystic ovary syndrome or androgen excess disorders appeared to be similar to those in the more comprehensive group.Previous findings linking androgen excess disorders to elevated uterine cancer risks might largely reflect underlying risk profiles.
View details for DOI 10.1016/j.fertnstert.2009.10.012
View details for Web of Science ID 000282160600040
View details for PubMedID 19939368
This study was undertaken to evaluate melanoma, thyroid, colon, and cervical cancer risks after clomiphene or gonadotropins.Retrospective cohort of 8422 women (155,527 women-years) evaluated for infertility (1965-1988). Through 1999, cancers were ascertained by questionnaire, cancer and death registries. Poisson regression estimated adjusted rate ratios (RRs).Clomiphene use did not significantly increase risk of melanoma (RR=1.66; 95% CI, 0.9-3.1), thyroid (RR=1.42; 95% CI, 0.5-3.7), cervical (RR=1.61; 95% CI, 0.5-4.7), or colon cancer (RR=0.83; 95% CI, 0.4-1.9). We found no relationship between clomiphene dose or cycles of use and cancer risk at any site. Clomiphene use may impart stronger effects on risks of melanoma (RR=2.00; 95% CI, 0.9-4.6) and thyroid cancer among women who remained nulliparous (RR=4.23; 95% CI, 1.0-17.1). Gonadotropins did not increase cancer risk for these sites.Fertility drugs do not appear to have strong effects on these cancers. Nonetheless, follow-up should be pursued to assess long-term risks and to monitor effects among women who remain nulliparous.
View details for DOI 10.1016/j.ajog.2005.01.091
View details for Web of Science ID 000232013300011
View details for PubMedID 16150258
Clomiphene citrate, a selective estrogen receptor modulator, increases estradiol levels and consequently may increase risk of cancer of the uterine corpus. The authors conducted a retrospective cohort study of 8,431 US women (145,876 woman-years) evaluated for infertility during 1965-1988. Through 1999, 39 uterine cancers were ascertained by questionnaire or cancer and death registries. Poisson regression estimated adjusted rate ratios. Study results suggest that clomiphene may increase uterine cancer risk (rate ratio (RR) = 1.79, 95% confidence interval (CI): 0.9, 3.4) and present evidence of a dose response (p(trend) = 0.07) and latency effect (p(trend) = 0.04). Uterine cancer risk increased with clomiphene dose (RR = 1.93, 95% CI: 0.9, 4.0 for >900 mg), menstrual cycles of use (RR = 2.16, 95% CI: 0.9, 5.2 for >or=6 cycles), and time elapsed since initial use (RR = 2.50, 95% CI: 0.9, 7.2 for women followed for >or=20 years). Risk was more strongly associated with clomiphene among nulligravid (RR = 3.49, 95% CI: 1.3, 9.3) and obese (RR = 6.02, 95% CI: 1.2, 30.0) women, with risk substantially elevated among women who were both obese and nulligravid (RR = 12.52, 95% CI: 1.5, 108.0). Clomiphene may increase uterine cancer risk, with higher doses leading to higher risk. Long-term follow-up of infertility cohorts is necessary to clarify the association between clomiphene use and uterine cancer.
View details for Web of Science ID 000227954600001
View details for PubMedID 15781949
To review and critique the literature regarding ovulation induction and cancer risk.Identification of relevant clinical and epidemiological literature through PubMed and other sources.Ovulation and associated hormonal changes have been linked with selected cancers, raising concerns regarding ovulation-inducing agents. Clinical studies have suggested potential links, but more definitive analytic investigations have been difficult to interpret given the small numbers, short follow-up, and imprecise information on drugs or indications for usage. Prospective studies have been limited by inabilities to control for other cancer predictors (including parity), while selective recall has been a concern for retrospective studies. Reports of large increases in ovarian cancer risk associated with fertility medications have not been replicated by more recent investigations. Some findings, based on small numbers, suggest slight increases in risk associated with fertility drugs among nulligravid women or after extended follow-up or for certain tumor subtypes, but further replication is needed. Fewer studies have assessed relationships with other hormonally related cancers, but limited findings support the need for further monitoring of long-term effects for breast and endometrial cancers. Findings regarding other cancers are extremely limited but should be pursued for cancers showing evidence of hormonal influences, including colon cancers and melanomas.
View details for DOI 10.1016/j.fertnstert.2004.09.016
View details for Web of Science ID 000227055400001
View details for PubMedID 15705362
The results of the study of endometrial biopsy for the diagnosis of infertility, which appear in this issue, are valid. Likelihood ratios and the receiver operating characteristic curves indicate that an out-of-phase test result is worse than useless; it is misleading.
View details for DOI 10.1016/j.fertnstert.2004.05.082
View details for Web of Science ID 000225128300005
View details for PubMedID 15533343
Despite the recognized role of hormones in the aetiology of breast cancer, there has been little evaluation of hormonal preparations used to treat infertility.A retrospective cohort study of 12,193 women evaluated for infertility between 1965 and 1988 at five clinical sites identified 292 in situ and invasive breast cancers in follow-up through 1999. Standardized incidence ratios (SIRs) compared breast cancer risks with those of the general population. Analyses within the cohort estimated rate ratios (RRs) associated with medications after adjustment for other breast cancer predictors.Infertile patients had a significantly higher breast cancer risk than the general population [SIR = 1.29, 95% confidence interval (CI) 1.1-1.4]. Analyses within the cohort showed adjusted RRs of 1.02 for clomiphene citrate and 1.07 for gonadotrophins, and no substantial relationships to dosage or cycles of use. Slight and non-significant elevations in risk were seen for both drugs after > or = 20 years of follow-up (RRs = 1.39 for clomiphene and 1.54 for gonadotrophins). However, the risk associated with clomiphene for invasive breast cancers was statistically significant (RR = 1.60, 95% CI 1.0-2.5).Although there was no overall increase in breast cancer risk associated with use of ovulation-stimulating drugs, long-term effects should continue to be monitored.
View details for DOI 10.1093/humrep/deh371
View details for Web of Science ID 000223792100015
View details for PubMedID 15217997
To evaluate the risk of ovarian cancer as related to underlying causes of infertility.Retrospective observational cohort study.Five large reproductive endocrinology practices.A total of 12,193 women evaluated for infertility between 1965 and 1988.None.Ovarian cancer ascertained through 1999.With 45 identified ovarian cancers, this cohort of infertility patients demonstrated a significantly higher rate of ovarian cancer than the general female population (standardized incidence ratio [SIR] = 1.98; 95% confidence interval [CI], 1.4-2.6). The risk was higher for patients with primary infertility (SIR = 2.73) than for those with secondary infertility (SIR = 1.44), and it was particularly high for patients who never subsequently conceived (SIR = 3.33). Women with endometriosis had the highest risk (SIR = 2.48; 95% CI, 1.3-4.2), with a further elevated risk among those with primary infertility (4.19, 2.0-7.7). Comparisons among the infertile women, which allowed calculation of rate ratios (RRs) after adjustment for multiple factors, also showed links with endometriosis. Compared with women with secondary infertility without endometriosis, patients with primary infertility and endometriosis had a RR of 2.72 (95% CI, 1.1-6.7).Determination of ovarian cancer risk should take into account the type of infertility (primary vs. secondary) and underlying causes. Further study of endometriosis may provide insights into ovarian carcinogenesis.
View details for DOI 10.1016/j.fertnstert.2004.02.109
View details for Web of Science ID 000223263000024
View details for PubMedID 15302291
Doctors who deal with individual patients fail to avoid interventions with minimal expected benefits. This is one reason that the United States spends more on health care services than any of 28 other industrialized nations. Yet, our money has not bought us health; our infant mortality rate ranks 23rd, and our overall life expectancy rate ranks 20th among the 29 nations. Ours is the only nation without a national health system. Our job-based health insurance system has allowed the number of uninsured persons to reach 44 million, which is 18% of the nonelderly population. This article examines the role of such ethical concepts as beneficence, utilitarianism, and justice in the allocation of health care resources. It also examines the innovative Oregon Health Plan and its use of cost-effectiveness analysis for health care allocation that is based on league tables.
View details for DOI 10.1016/j.ajog.2004.02.054
View details for Web of Science ID 000222414100042
View details for PubMedID 15284761
Reappraisal of current guidelines mandating frozen-thawed semen.Cost-effectiveness analysis comparing the use of frozen semen with the use of fresh semen from the same donors without a second antibody test.A Markov model computer simulation.A theoretical cohort of 80000 women whose husbands are azoospermic.Simulation with calculation of costs and payoffs.Total lifetime direct health care costs, costs per live birth, life expectancy, quality adjusted life years (QALY), marginal cost effectiveness (dollar/QALY).If all 80000 women who undergo donor insemination in the United States each year chose to use fresh semen from donors screened according to the current practice guidelines but without semen cryopreservation, there would be 8881 more births and the mean cost per live birth would be US dollars 15501 less. One recipient would become infected with HIV-1 every 5.1 years, during which time over 180000 noninfected children would be born. The average life expectancy of recipients would be reduced by 2 days, but their quality-adjusted life expectancy would increase by over 1 month. Medicolegal costs to physicians would need to exceed US dollars 780 million per infection to equalize the cost effectiveness of the fresh and frozen policies.The guidelines should be revised to allow the use of fresh semen by informed recipients.
View details for DOI 10.1016/j.fertnstert.2003.06.003
View details for Web of Science ID 000187969500017
View details for PubMedID 14711548
Development of an endometriosis classification system based on empirically derived stages of the disease, to supplant the Acosta (1973), Kistner (1977), and American Fertility Society (1985) classifications, which are based on arbitrarily defined stages and often fail to predict pregnancy rates.Retrospective cohort analysis.University infertility clinic.Women with endometriosis and > or = 1 year of infertility. Diagnosis of endometriosis was made by direct visualization, with type of lesion (implant or adhesion) at multiple sites recorded; total of 202 patients. All diagnosed infertility problems were treated based on semen analysis, postcoital test, and endometrial biopsy. Pregnancy rates were analyzed by life-table and cluster analyses, and combinations of site and type were also analyzed by Cox's regression model.No individual anatomic site or type significantly affected prognosis, nor was any cluster useful for predicting outcome.Anatomic site and type of lesion are insufficient for predicting fertility when used as sole components of a clinical staging system for endometriosis.
View details for Web of Science ID A1993LN70600007
View details for PubMedID 8401684
View details for Web of Science ID A1989AF34800008
The authors examined the results of the initial semen analysis from 1089 couples in an infertility clinic. The distributions of the values for various semen variables among couples who remained infertile were very similar to those among couples who later conceived. A cutoff point was selected in each pair of distributions to compare the cumulative probability of conception for couples with higher and lower results. The authors took into account the varying times to conception or loss to follow-up by using life table analysis. No statistically significant differences were found at the P = 0.05 level of significance. Cox's univariate and multiple regression models were then used to investigate the relationship between various semen characteristics and future fertility. Finding no significant influence of any semen characteristic on the cumulative probability of conception, the authors believe that using specific values of the semen analysis to estimate the potential for fertility of infertile couples is not useful.
View details for Web of Science ID A1988N785600022
View details for PubMedID 3371484
Development of techniques for cryopreservation of embryos of several species, principally the mouse, laid the foundation for cryopreservation of human embryos. As IVF has become more widely available and the need for the cryopreservation of human embryos has become apparent, pressure for technical development has increased. The ideal method would be simple, inexpensive, and effective. The most effective method for cryopreservation of early human embryos, such as those at the 1-cell pronuclear stage and up to the 4-cell stage, now appears to be stepwise cooling in 1,2-propanediol with sucrose in plastic ministraws. The preferred method for intermediate stage embryos uses DMSO with cooling and thawing at slow rates in a programmed biologic freezer. For the human blastocyst, slow cooling in glycerol and rapid thawing is the only method reported with survival rates comparable to those achieved for intermediate stage embryos using DMSO. The rates of survival from freezing and thawing blastocysts are not sufficiently high, however, to justify the losses associated with prolonged in vitro incubation. Even at the current level of technical achievement, cryopreservation of human embryos provides the clearest opportunity to improve the clinical results obtained with IVF. Research now underway in the modification of methods for vitrification and ultrarapid freezing holds promise for both simplification of technology and improvement of outcome. In view of legal and ethical considerations involved in embryo preservation, the desirability of ova preservation is widely accepted. Although a small number of human unfertilized mature ova have been cryopreserved using various methods, success rates are still low. Methods for the cryopreservation of eggs should be developed, but these methods probably should be proved by animal experiments to be safe, especially with regard to genetic damage, before a policy of transfer of embryos derived from frozen-thawed human ova is applied on a large scale.
View details for Web of Science ID A1988N360900001
View details for PubMedID 3282929
In a multicenter trial involving 11 centers, 160 women were enrolled to evaluate the safety and effectiveness of 1 or 2 gm of cefotetan administered every 12 hours in the treatment of obstetric and gynecologic infections. The 133 evaluable patients generally were under 25 years of age, were nonwhite, and had hospital-acquired endometritis or pelvic inflammatory disease caused by both aerobic and anaerobic bacteria. Escherichia coli, Neisseria gonorrhoeae, group D streptococci, Bacteroides sp., and Peptococcus sp. were among the most frequently isolated pathogens. The patients were treated for a mean of 5.6 +/- 1.6 days and received a total dose of 19.27 gm. The signs and symptoms of infection were cleared or improved in 93% of the 133 patients evaluable for clinical response. Of the 116 evaluated bacteriologically, 95% had a satisfactory or presumed satisfactory response; only six patients (5%) were considered to be bacteriologic failures. Differences in the results of several clinical laboratory tests performed before and after treatment were statistically, but not clinically, significant (p less than 0.05). Safety was evaluated in the 158 patients who received cefotetan, and only four (3%) had adverse reactions considered related to the drug. Cefotetan was clearly effective and produced no untoward reactions in these women with obstetric and gynecologic infections caused by both aerobic and anaerobic organisms when administered at 1 or 2 gm every 12 hours.
View details for Web of Science ID A1988M709200007
View details for PubMedID 3162652
Cryopreservation of unfertilized mouse ova and 2-cell embryos by a vitrification technique was examined. Survival was defined by development to the hatching blastocyst stage after in vitro fertilization. With 19 embryos at the 2-cell stage, the authors obtained 100% morphologic survival and 89% development to hatching blastocyst stage. To define the optimal conditions for vitrification of ova, the authors treated a total of 845 unfertilized ova. In experiments done at 0 degree C, the concentration of vitrification solution (VS1) and the length of exposure of ova to VS1 both had significant (P less than 0.01) effects on survival. The mean survival rate for controls in ten experiments was 52%. VS1 100% or 90% in HEPES buffered saline and 10 minutes' exposure yielded rates that did not differ significantly from controls. Significantly lower survival rates followed the use of 70 and 80% solution and exposure for 5, 15, 20, or 30 minutes. Thus, under these conditions, exposure of unfertilized mouse ova to VS1 and cooling to 0 degree C did not interfere with in vitro fertilization and development of embryos. However, in five experiments in which a total of 101 ova were plunged into liquid nitrogen after treatment with VS1 under the optimal conditions, none could be fertilized in vitro.
View details for Web of Science ID A1987J603100023
View details for PubMedID 3609342
An immunoradiometric assay and a radioimmunoassay (RIA) were used to quantitate human chorionic gonadotropin (hCG) in the sera of ten pregnant women at term and of six women with gestational trophoblastic neoplasia. The two techniques show good correlation (Pearson correlation coefficient .96) in the assay of pregnancy serum. Because only the RIA, and not the immunoradiometric assay, measures the free beta-subunit of hCG, a comparison of the results obtained by the two immunoassay methods permits a semi-quantitative assessment of the free beta-subunit. The numerical results may not reflect the actual concentration of free beta-subunit in that two different immunoassay methods are used.
View details for Web of Science ID A1985AEG9600020
View details for PubMedID 2580254
An immunoradiometric assay (IRMA) for the quantitative analysis of human chorionic gonadotropin (hCG) was evaluated for specificity, sensitivity, accuracy and precision. The results were compared with those of the conventional radioimmunoassay (RIA) used in our laboratory. The IRMA is a solid-phase, double-antibody immunoassay that sandwiches the intact hCG molecule between the two antibodies. It has specificity, accuracy, and precision which are similar to those of the RIA. The RIA is based upon the assumptions that the antigenicity of the tracer is not altered by the iodination process and that the antibody reacts equally with all of the antigens, including the radiolabeled antigen. The IRMA does not use radiolabeled antigens and thus is free of the assumptions made in the conventional RIA. The IRMA may be more accurate at the lower limits of the assay because it does not require logarithmic transformations. Since the IRMA does not measure the free beta-subunit of hCG, it cannot be endorsed as the sole technique to quantitate hCG in patients with gestational trophoblastic neoplasia until the significance of the free beta-subunit in these patients is determined.
View details for Web of Science ID A1984RZ07900014
View details for PubMedID 6691384
This study develops a method of identifying factors that predict pregnancy rates in patients with endometriosis. In 123 women, 60% had adhesions, 89% had implants, and 29% had endometriomas. The most common lesions were cul-de-sac implants (60%), ovarian implants (58%), and ovarian adhesions (55%). With no treatment, the life-table-estimated 3-year pregnancy rate was 40%; with oral contraceptives, 33%; and with surgery, 53%. Clustering techniques suggested new combinations of variables to be tested. We identified structures commonly involved simultaneously in a given patient, defined subgroups based on type of lesion, and developed a method to determine which factors were important in predicting outcome. In our patients, neither of two current methods of endometriosis staging predicted outcome. Further testing of the model systems suggested by the data may enable us to develop a staging system more predictive of pregnancy rates in endometriosis patients.
View details for Web of Science ID A1982PT96300003
View details for PubMedID 7141007
A hypothesis derived from the old wives' tale that adoption increases subsequent fertility was tested by analysis of follow-up data obtained from 895 couples who were "at risk" of pregnancy and of adoption after they had registered in the Stanford Infertility Clinic between 1963 and 1977. Of the 767 couples who did not adopt, 329 later conceived; of the 128 who did adopt, 41 later conceived. Simple comparison of the percentages or, indeed, of the life tables suggests reduced fertility after adoption. However, this is probably a spurious effect related to a number of factors which differ between two groups. These differences were controlled in the statistical analysis by methods which take into account the length of time each couple was at risk of either conception or adoption and the presence or absence of explanatory variables. The relative risk of conception estimated by the Cox model was not significantly different from 1 and the Mantel-Haenszel statistic (m = 0.208) indicates no significant difference in subsequent conception rates between adoptive and not-adoptive couples. The same methods were used to control for seven covariates, including age and duration of infertility, which could affect conception rates. In each instance, the estimate of relative risk of conception for adoptive versus not-adoptive couples was not significantly different from 1. Therefore, our data do not support the hypothesis that adoption affects subsequent fertility.
View details for Web of Science ID A1979GW22400005
View details for PubMedID 453239
This study was undertaken to determine the prevalence of radiologically detectable pituitary tumors among patients seen initially in a gynecology clinic for a complaint of secondary amenorrhea. In a group of 144 women with secondary amenorrhea of more than 6 months' duration, 13 had radiologic abnormalities of the sella turcica detectable with standard skull films without tomography. These gynecologic patients composed more than half of the women in the reproductive age group who were diagnosed at this medical center as having a pituitary tumor. Only one patient with oligomenorrhea or secondary amenorrhea of less than 2 years' duration had a detectable tumor. Thus, for patients with short-term amenorrhea, the risk of having a pituitary tumor is small, especially in the absence of galactorrhea, headache, or changes in vision. However, 12 of 71 patients with amenorrhea longer than 2 years (17%) had detectable tumors and the risk appears to increase progressively with time. Assay of adrenal and thyroid hormones did not discriminate between patients with and without pituitary tumors. Early detection of these tumors is aided by serial sella x-rays, tomograms, prolactin assays, and newer pituitary function tests. Patients presenting with postpill amenorrhea and postpartum amenorrhea illustrate the hazard of interpreting a temporal relationship as a causal one.
View details for Web of Science ID A1976BY62300006
View details for PubMedID 937401
A modified surgical technique, using separate incisions for vulvectomy and for each groin, resulted in a low morbidity rate, with no increase in tumor recurrence and no reduction in length of survival time in comparison with previously reported methods of treatment of invasive squamous carcinoma of the vulva. The clinical staging adopted by the International Federation of Gynaecology and Obstetrics accurately predicted survival time for patients in this series as in others. However, in instances in which the histologic status of the nodes differs from the clinical assessment, postsurgical staging with primary importance attached to the histologic evaluation more accurately predicts prognosis.
View details for Web of Science ID A1975V134300017
View details for PubMedID 1209475