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Background: Chlamydial infection is associated with tubal factor infertility (TFI); however, assessment of prior chlamydial infection and TFI is imperfect. We previously evaluated a combination of serological assays for association with TFI. We now describe the chlamydial contribution to TFI using a newer Chlamydia trachomatis Pgp3-enhanced serological (Pgp3) assay., Methods: In our case-control study of women 19 to 42 years old with hysterosalpingogram-diagnosed TFI (cases) and non-TFI (controls) in 2 US infertility clinics, we assessed possible associations and effect modifiers between Pgp3 seropositivity and TFI using adjusted odds ratios with 95% confidence intervals (CIs) stratified by race. We then estimated the adjusted chlamydia population-attributable fraction with 95% CI of TFI., Results: All Black (n = 107) and 618 of 620 non-Black women had Pgp3 results. Pgp3 seropositivity was 25.9% (95% CI, 19.3%-33.8%) for non-Black cases, 15.2% (95% CI, 12.3%-18.7%) for non-Black controls, 66.0% (95% CI, 51.7%-77.8%) for Black cases, and 71.7% (95% CI, 59.2%-81.5%) for Black controls. Among 476 non-Black women without endometriosis (n = 476), Pgp3 was associated with TFI (adjusted odds ratio, 2.6 [95% CI, 1.5-4.4]), adjusting for clinic, age, and income; chlamydia TFI-adjusted population-attributable fraction was 19.8% (95% CI, 7.7%-32.2%) in these women. Pgp3 positivity was not associated with TFI among non-Black women with endometriosis or among Black women (regardless of endometriosis)., Conclusions: Among non-Black infertile women without endometriosis in these clinics, 20% of TFI was attributed to chlamydia. Better biomarkers are needed to estimate chlamydia TFI PAF, especially in Black women., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no conflict of interest. This study was supported by Centers for Disease Control and Prevention, Prevention Research Centers grants (5U48DP001915 and 5U48DP001918) and National Institutes of Health, Sexually Transmitted Infections Clinical Trials group (contract HHSN27220130012I)., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Nearly 14% of US women report any lifetime infertility which is associated with health care costs and psychosocial consequences. Tubal factor infertility (TFI) often occurs as a result of sexually transmitted diseases and subsequent pelvic inflammatory disease. We sought to evaluate for and describe potential racial disparities in TFI and in vitro fertilization (IVF) prevalence., Methods: Records of women aged 19 to 42 years in our retrospective cohort from 2 US infertility clinics were reviewed. We calculated TFI prevalence, IVF initiation prevalence, and prevalence ratios (PRs), with 95% confidence intervals (CIs) for each estimate, overall and by race., Results: Among 660 infertile women, 110 (16.7%; 95% CI, 13.8-19.5%) had TFI which was higher in Black compared with White women (30.3% [33/109] vs 13.9% [68/489]; PR, 2.2 [95% CI, 1.5-3.1]). For women with TFI, IVF was offered to similar proportions of women by race (51.5% [17/33] vs 52.9% [36/68] for Black vs White women); however, fewer Black than White women with TFI started IVF (6.7% [1/15] vs 31.0% [9/29]; PR, 0.2 [95% CI, 0-1.0]), although the difference was not statistically different., Conclusions: Tubal factor infertility prevalence was 2-fold higher among Black than White women seeking care for infertility. Among women with TFI, data suggested a lower likelihood of Black women starting IVF than White women. Improved sexually transmitted disease prevention and treatment might ameliorate disparities in TFI., Competing Interests: Conflicts of Interest: K.R.H. is on the Speakers bureau for AbbVie, and W.M.G. has received research funds and consulting fees from Hologic and consulting fees from Roche. The other authors declare no conflicts of interest., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Chlamydia trachomatis (Ct) infection ascending to the upper genital tract can cause infertility. Direct association of genetic variants as contributors is challenging because infertility may not be diagnosed until years after infection. Investigating the intermediate trait of ascension bridges this gap., Methods: We identified infertility genome-wide association study (GWAS) loci using deoxyribonucleic acid from Ct-seropositive cisgender women in a tubal factor infertility study and Ct-infected cisgender women from a longitudinal pelvic inflammatory disease cohort with known fertility status. Deoxyribonucleic acid and blood messenger ribonucleic acid from 2 additional female cohorts with active Ct infection and known endometrial infection status were used to investigate the impact of infertility single-nucleotide polymorphisms (SNPs) on Ct ascension. A statistical mediation test examined whether multiple infertility SNPs jointly influenced ascension risk by modulating expression of mediator genes., Results: We identified 112 candidate infertility GWAS loci, and 31 associated with Ct ascension. The SNPs altered chlamydial ascension by modulating expression of 40 mediator genes. Mediator genes identified are involved in innate immune responses including type I interferon production, T-cell function, fibrosis, female reproductive tract health, and protein synthesis and degradation., Conclusions: We identified Ct-related infertility loci and their potential functional effects on Ct ascension., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population-attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiological studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared with White women but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility., Objectives: The objectives of the study were to estimate the population-attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (Black, non-Black) and assess how different definitions of Chlamydia trachomatis seropositivity and tubal factor infertility affect population-attributable fraction estimates., Study Design: We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL, and Pittsburgh, PA, during October 2012 through June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of 1 and 3 controls per case for Black and non-Black women, respectively. We assessed Chlamydia trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated Chlamydia trachomatis seropositivity and calculated Chlamydia trachomatis-tubal factor infertility odds ratios and population-attributable fraction, stratified by race., Results: We enrolled 107 Black women (47 cases, 60 controls) and 620 non-Black women (140 cases, 480 controls). Chlamydia trachomatis seropositivity by either assay was 81% (95% confidence interval, 73-89%) among Black and 31% (95% confidence interval, 28-35%) among non-Black participants (P < .001). Using the primary Chlamydia trachomatis seropositivity and tubal factor infertility definitions, no significant association was detected between chlamydia and tubal factor infertility among Blacks (odds ratio, 1.22, 95% confidence interval, 0.45-3.28) or non-Blacks (odds ratio, 1.41, 95% confidence interval, 0.95-2.09), and the estimated population-attributable fraction was 15% (95% confidence interval, -97% to 68%) among Blacks and 11% (95% confidence interval, -3% to 23%) among non-Blacks. Use of alternate serological measures and tubal factor infertility definitions had an impact on the magnitude of the chlamydia-tubal factor infertility association and resulted in a significant association among non-Blacks., Conclusion: Low population-attributable fraction estimates suggest factors in addition to chlamydia contribute to tubal factor infertility in the study population. However, high background Chlamydia trachomatis seropositivity among controls, most striking among Black participants, could have obscured an association with tubal factor infertility and resulted in a population-attributable fraction that underestimates the true etiological role of chlamydia. Choice of chlamydia and tubal factor infertility definitions also has an impact on the odds ratio and population-attributable fraction estimates., (Published by Elsevier Inc.)

Context: Experimental evidence supports a relevance of vitamin D (VitD) for reproduction; however, data in humans are sparse and inconsistent., Objective: To assess the relationship of VitD status with ovulation induction (OI) outcomes in women with polycystic ovary syndrome (PCOS)., Design: A retrospective cohort., Setting: Secondary analysis of randomized controlled trial data., Participants: Participants in the Pregnancy in PCOS I (PPCOS I) randomized controlled trial (n = 540) met the National Institutes of Health diagnostic criteria for PCOS., Interventions: Serum 25OHD levels were measured in stored sera., Main Outcome Measures: Primary, live birth (LB); secondary, ovulation and pregnancy loss after OI., Results: Likelihood for LB was reduced by 44% for women if the 25OHD level was < 30 ng/mL (<75 nmol/L; odds ratio [OR], 0.58 [0.35-0.92]). Progressive improvement in the odds for LB was noted at thresholds of ≥38 ng/mL (≥95 nmol/L; OR, 1.42 [1.08-1.8]), ≥40 ng/mL (≥100 nmol/L; OR, 1.51 [1.05-2.17]), and ≥45 ng/mL (≥112.5 nmol/L; OR, 4.46 [1.27-15.72]). On adjusted analyses, VitD status was an independent predictor of LB and ovulation after OI., Conclusions: In women with PCOS, serum 25OHD was an independent predictor of measures of reproductive success after OI. Our data identify reproductive thresholds for serum 25OHD that are higher than recommended for the nonpregnant population.

Objective: To determine the proportion of euthyroid women attending a fertility practice who develop hypothyroidism in very early pregnancy (gestational hypothyroidism [GHT]), and to examine the association of GHT with exogenous gonadotropin treatment., Design: Retrospective cohort study., Setting: A private reproductive medicine practice., Patient(s): All healthy women (N = 94) with infertility or recurrent pregnancy loss, TSH level <2.5 mIU/L, negative thyroid peroxidase antibodies at initial evaluation, and not taking thyroid medication, who conceived during an 18-month period., Intervention(s): Usual fertility care; 30 women who had received exogenous gonadotropins., Main Outcome Measure(s): Serum TSH level at the time of pregnancy detection., Result(s): Gestational hypothyroidism (TSH ≥ 2.5 mIU/L) developed in 23 of 94 women (24%). The mean increase in serum TSH level from initial evaluation to early pregnancy was 0.45 ± 0.08 [SE] mIU/L. There was a trend toward the association of GHT with use of exogenous gonadotropins. Gestational hypothyroidism was positively associated with initial prepregnancy TSH level., Conclusion(s): Euthyroid women may develop mild hypothyroidism in early pregnancy, especially after exogenous gonadotropin treatment. Appropriate vigilance will allow for timely levothyroxine treatment., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Study Question: Do women with polycystic ovary syndrome (PCOS) seeking fertility treatment report smoking accurately and does participation in infertility treatment alter smoking?, Summary Answer: Self-report of smoking in infertile women with PCOS is accurate (based on serum cotinine levels) and smoking is unlikely to change over time with infertility treatment., What Is Known Already: Women with PCOS have high rates of smoking and it is associated with worse insulin resistance and metabolic dysfunction., Study Design, Size, Duration: Secondary study of smoking history from a large randomized controlled trial of infertility treatments in women with PCOS (N = 626) including a nested case-control study (N = 148) of serum cotinine levels within this cohort to validate self-report of smoking., Participants/materials, Setting, Methods: Women with PCOS, age 18-40, seeking fertility who participated in a multi-center clinical trial testing first-line ovulation induction agents conducted at academic health centers in the USA., Main Results and the Role of Chance: Overall, self-report of smoking in the nested case-control study agreed well with smoking status as determined by measure of serum cotinine levels, at 90% or better for each of the groups at baseline (98% of never smokers had cotinine levels <15 ng/ml compared with 90% of past smokers and 6% of current smokers). There were minor changes in smoking status as determined by serum cotinine levels over time, with the greatest change found in the smoking groups (past or current smokers). In the larger cohort, hirsutism scores at baseline were lower in the never smokers compared with past smokers. Total testosterone levels at baseline were also lower in the never smokers compared with current smokers. At end of study follow-up insulin levels and homeostatic index of insulin resistance increased in the current smokers (P < 0.01 for both) compared with baseline and with non-smokers. The chance for ovulation was not associated with smoking status, but live birth rates were increased (non-significantly) in never or past smokers., Limitations, Reasons for Caution: The limitations include the selection bias involved in our nested case-control study, the possibility of misclassifying exposure to second hand smoke as smoking and our failure to capture self-reported changes in smoking status after enrollment in the trial., Wider Implications of the Findings: Because self-report of smoking is accurate, further testing of smoking status is not necessary in women with PCOS. Because smoking status is unlikely to change during infertility treatment, extra attention should be focused on smoking cessation in current or recent smokers who seek or who are receiving infertility treatment., Study Funding/competing Interests: Sponsored by the Eugene Kennedy Shriver National Institute of Child Health and Human Development of the U.S. National Institutes of Health., Clinical Trial Registration Numbers: ClinicalTrials.gov numbers, NCT00068861 and NCT00719186., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Many women with polycystic ovary syndrome (PCOS) experience infertility and hirsutism and often seek treatment for both concurrently. We investigated whether women who ovulate in response to treatment with clomiphene citrate, metformin, or both would have greater improvement in hirsutism compared with those who did not ovulate., Methods: This is a secondary analysis evaluating the change in Ferriman-Gallwey score for the hirsute women (n=505 [80.7%]) from the Pregnancy in Polycystic Ovary Syndrome I study. This was a prospective, randomized, doubled-blind trial of 626 women with PCOS and infertility recruited from 12 university sites. They were treated with clomiphene citrate, metformin, or both (combination) for up to six cycles, and hirsutism evaluators were blinded to group assignment., Results: There was a significant decrease in the Ferriman-Gallwey score between baseline and completion of the study in each of the three individual groups (clomiphene citrate, P=.024; metformin, P=.005; combination, P<.001). There was no significant difference in the degree to which the hirsutism score changed when comparing the three groups (P=.44). The change in hirsutism was not associated with the duration of treatment or with the presence or absence of ovulation., Conclusion: In infertile hirsute women with PCOS, treatment with clomiphene citrate, metformin, or both for up to six cycles does not alter hirsutism., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00068861., Level of Evidence: II.

Objective: To estimate whether progestin-induced endometrial shedding, before ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS)., Methods: A secondary analysis of the data from 626 women with PCOS from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed)., Results: Although ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live births per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; P<.001). The difference was more marked when rate was calculated per ovulation (live births per ovulation: spontaneous menses 3.0%; anovulatory with progestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; P<.001)., Conclusion: Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared with anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin before ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS., Level of Evidence: II.

Background: Although histological dating of endometrial biopsies provides little help for prediction or diagnosis of infertility, analysis of individual endometrial proteins, proteomic profiling and transcriptome analysis have suggested several biomarkers with altered expression arising from intrinsic abnormalities, inadequate stimulation by or in response to gonadal steroids or altered function due to systemic disorders. The objective of this study was to delineate the developmental dynamics of potentially important proteins in the secretory phase of the menstrual cycle, utilizing a collection of endometrial biopsies from women of fertile (n = 89) and infertile (n = 89) couples., Methods and Results: Progesterone receptor-B (PGR-B), leukemia inhibitory factor, glycodelin/progestagen-associated endometrial protein (PAEP), homeobox A10, heparin-binding EGF-like growth factor, calcitonin and chemokine ligand 14 (CXCL14) were measured using a high-throughput, quantitative immunohistochemical method. Significant cyclic and tissue-specific regulation was documented for each protein, as well as their dysregulation in women of infertile couples. Infertile patients demonstrated a delay early in the secretory phase in the decline of PGR-B (P < 0.05) and premature mid-secretory increases in PAEP (P < 0.05) and CXCL14 (P < 0.05), suggesting that the implantation interval could be closing early. Correlation analysis identified potential interactions among certain proteins that were disrupted by infertility., Conclusions: This approach overcomes the limitations of a small sample number. Protein expression and localization provided important insights into the potential roles of these proteins in normal and pathological development of the endometrium that is not attainable from transcriptome analysis, establishing a basis for biomarker, diagnostic and targeted drug development for women with infertility.

Context: Nonalcoholic fatty liver disease is common to insulin-resistant states such as polycystic ovary syndrome (PCOS). Metformin (MET) is often used to treat PCOS but information is limited as to its effects on liver function., Objective: We sought to determine the effects of MET on serum hepatic parameters in PCOS patients., Design: This was a secondary analysis of a randomized, doubled-blind trial from 2002-2004., Setting: This multi-center clinical trial was conducted in academic centers., Patients: Six hundred twenty-six infertile women with PCOS with serum liver function parameters less than twice the upper limit of normal were included., Interventions: Clomiphene citrate (n = 209), MET (n = 208), or combined (n = 209) were given for up to 6 months., Main Outcome Measure: The percent change from baseline in renal and liver function between- and within-treatment arms was assessed., Results: Renal function improved in all treatment arms with significant decreases in serum blood urea nitrogen levels (range, -14.7 to -21.3%) as well as creatinine (-4.2 to -6.9%). There were similar decreases in liver transaminase levels in the clomiphene citrate and combined arms (-10% in bilirubin, -9 to -11% in transaminases) without significant changes in the MET arm. When categorizing baseline bilirubin, aspartate aminotransferase, and alanine aminotransferase into tertiles, there were significant within-treatment arm differences between the tertiles with the highest tertile having the largest decrease from baseline regardless of treatment arm., Conclusion: Women with PCOS can safely use metformin and clomiphene even in the setting of mildly abnormal liver function parameters, and both result in improved renal function.

Context: There is no standardized assay of testosterone in women. Liquid chromatography mass spectrometry (LC/MS) has been proposed as the preferable assay by an Endocrine Society Position Statement., Objective: The aim was to compare assay results from a direct RIA with two LC/MS., Design and Setting: We conducted a blinded laboratory study including masked duplicate samples at three laboratories--two academic (University of Virginia, RIA; and Mayo Clinic, LC/MS) and one commercial (Quest, LC/MS)., Participants and Interventions: Baseline testosterone levels from 596 women with PCOS who participated in a large, multicenter, randomized controlled infertility trial performed at academic health centers in the United States were run by varying assays, and results were compared., Main Outcome Measure: We measured assay precision and correlation and baseline Ferriman-Gallwey hirsutism scores., Results: Median testosterone levels were highest with RIA. The correlations between the blinded samples that were run in duplicate were comparable. The correlation coefficient (CC) between LC/MS at Quest and Mayo was 0.83 [95% confidence interval (CI), 0.80-0.85], between RIA and LC/MS at Mayo was 0.79 (95% CI, 0.76-0.82), and between RIA and LC/MS at Quest was 0.67 (95% CI, 0.63-0.72). Interassay variation was highest at the lower levels of total testosterone (≤50 ng/dl). The CC for Quest LC/MS was significantly different from those derived from the other assays. We found similar correlations between total testosterone levels and hirsutism score with the RIA (CC=0.24), LC/MS at Mayo (CC=0.15), or Quest (CC=0.17)., Conclusions: A testosterone RIA is comparable to LC/MS assays. There is significant variability between LC/MS assays and poor precision with all assays at low testosterone levels.

Objective: To investigate the relationship among intercourse compliance, ovulation, and the occurrence of pregnancy in the Reproductive Medicine Network's Pregnancy in Polycystic Ovary Syndrome (RMNPPCOS) Trial., Design: Post hoc data analysis of subjects in the Reproductive Medicine Network PPCOS Trial., Setting: Academic medical centers., Intervention(s): None., Patient(s): Six hundred twenty-six infertile women with polycystic ovary syndrome with a mean age of 28.1+/-4 years and mean body mass index of 35.2+/-8.7 kg/m2., Main Outcome Measure(s): Intercourse compliance, ovulation, and pregnancy., Result(s): Data on 2925 cycles were included in the analysis, of which 1340 were ovulatory cycles and 1585 were nonovulatory cycles. The rates of intercourse compliance in the PPCOS trial were similar across all treatment groups at all cycles except cycle 4. Among cycles with known ovulation status, 81.2% of patients were compliant with intercourse instructions. Patients were more intercourse compliant in those cycles during which ovulation occurred (83.2% vs. 79.4%). With regard to ovulatory cycles, there was no difference in the occurrence of pregnancy when comparing intercourse compliant versus intercourse noncompliant cycles., Conclusion(s): Intercourse compliance was not associated with the occurrence of pregnancy in ovulatory cycles in the PPCOS Trial. The occurrence of ovulation still remains a critical predictor for the occurrence of pregnancy., (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship between body mass index and intercourse compliance in the Reproductive Medicine Network's Pregnancy in Polycystic Ovary Syndrome (RMN PPCOS) Trial., Design: Post hoc data analysis of subjects in the RMN PPCOS Trial., Setting: Academic medical centers., Intervention(s): None., Patient(s): Six hundred twenty-six infertile women with polycystic ovary syndrome (PCOS) with a mean age of 28.1+/-4 years and mean body mass index (BMI) of 35.2+/-8.7 kg/m2., Main Outcome Measure(s): Intercourse compliance and BMI., Result(s): Overall, body mass index was not associated with increased intercourse compliance. However, although patients with BMI>or=35 were less likely to ovulate than patients with BMI<35, they tend to be more compliant with intercourse frequency in ovulatory cycles than patients with BMI<35., Conclusion(s): BMI was not associated with intercourse compliance or noncompliance. An elevated BMI in infertile women with PCOS is not associated with poor intercourse compliance., (Copyright (c) 2010. Published by Elsevier Inc.)

Context: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The selection of first-line therapies for ovulation induction is empiric., Objective: The aim of the study was to develop a clinically useful predictive model of live birth with varying ovulation induction methods., Design, Setting, and Participants: We built four prognostic models from a large multicenter randomized controlled infertility trial of 626 women with PCOS performed at academic health centers in the United States to predict success of ovulation, conception, pregnancy, and live birth, evaluating the influence of patients' baseline characteristics., Interventions: Ovulation was induced with clomiphene, metformin, or the combination of both for up to six cycles or conception., Main Outcome Measure: The primary outcome of the trial was the rate of live births., Results: Baseline free androgen index, baseline proinsulin level, interaction of treatment arm with body mass index, and duration of attempting conception were significant predictors in all four models. History of a prior loss predicted ovulation and conception, but not pregnancy or live birth. A modified Ferriman Gallwey hirsutism score of less than 8 was predictive of conception, pregnancy, and live birth (although it did not predict ovulation success). Age was a divergent predictor based on outcome; age greater than 34 predicted ovulation, whereas age less than 35 was a predictive factor for a successful pregnancy and live birth. Smoking history had no predictive value., Conclusions: A live birth prediction chart developed from basic clinical parameters (body mass index, age, hirsutism score, and duration of attempting conception) may help physicians counsel and select infertility treatments for women with PCOS.

Objective: To evaluate the feasibility of robotic microsurgical tubal anastomosis and compare the results and cost effectiveness with the same procedure performed by laparotomy., Design: Prospective cohort study., Setting: University hospital., Patient(s): Patients with a history of bilateral tubal ligation who desired reversal for future fertility., Intervention(s): Tubal anastomoses through either a robotic approach or through a laparotomy., Main Outcome Measure(s): Operative times, hospitalization, complications, postoperative patency, clinical outcomes, and the cost per live birth., Result(s): The mean operative time for robotic anastomoses was statistically significantly greater than open anastomoses (ROBOT 201 minutes; OPEN 155.3 minutes), although hospitalization times were statistically significantly shorter (ROBOT 4 hours; OPEN 34.7 hours). The return to instrumental activities of daily living was accelerated in the patients who had undergone a robotic anastomosis (ROBOT 11.1 days; OPEN 28.1 days). Although this was a small series, the pregnancy rates were comparable between groups (ROBOT 62.5%; OPEN 50%), yet the rate of abnormal pregnancy was higher in the robotic group (ectopic: ROBOT 4, OPEN 1; spontaneous pregnancy loss: ROBOT 2, OPEN 1). The cost per delivery was similar between the groups (ROBOT $92,488.00, OPEN $92,205.90)., Conclusion(s): Robotically assisted laparoscopic microsurgical tubal anastomosis is feasible and cost effective with results that are comparable with the traditional open approach.

We investigated whether poor adherence with metformin tablets may have contributed to the poor success rates seen in the metformin-containing arms of the Pregnancy in Polycystic Ovary Syndrome (PPCOS) Trial. Median adherence for both metformin and clomiphene citrate tablets was within acceptable limits and unrelated to ovulation: thus, failure to comply with physician recommendations for metformin dosing was not the reason for low ovulation and pregnancy rates in the PPCOS Trial.

Context: When used for ovulation induction, higher doses of clomiphene may lead to antiestrogenic side effects that reduce fecundity. It has been suggested that metformin in combination with clomiphene can restore ovulation to some clomiphene-resistant anovulators with polycystic ovary syndrome (PCOS)., Objective: Our objective was to determine if cotreatment with extended-release metformin (metformin XR) can lower the threshold dose of clomiphene needed to induce ovulation in women with PCOS., Design: A secondary analysis of data from the National Institute of Child Health and Human Development Cooperative Multicenter Reproductive Medicine Network prospective, double-blind, placebo-controlled multicenter clinical trial, Pregnancy in Polycystic Ovary Syndrome, was performed., Setting: Study volunteers at multiple academic medical centers were included., Participants: Women with PCOS and elevated serum testosterone who were randomized to clomiphene alone or with metformin (n = 209 in each group) were included in the study., Interventions: Clomiphene citrate, 50 mg daily for 5 d, was increased to 100 and 150 mg in subsequent cycles if ovulation was not achieved; half also received metformin XR, 1000 mg twice daily. Treatment was for up to 30 wk or six cycles, or until first pregnancy., Main Outcome Measures: Ovulation was confirmed by a serum progesterone more than or equal to 5 ng/ml, drawn prospectively every 1-2 wk., Results: The overall prevalence of at least one ovulation after clomiphene was 75 and 83% (P = 0.04) for the clomiphene-only and clomiphene plus metformin groups, respectively. Using available data from 314 ovulators, the frequency distribution of the lowest clomiphene dose (50, 100, or 150 mg daily) resulting in ovulation was indistinguishable between the two treatment groups., Conclusion: Metformin XR does not reduce the lowest dose of clomiphene that induces ovulation in women with PCOS.

Context: Clomiphene and insulin sensitizers such as metformin are used to induce ovulation in polycystic ovary syndrome (PCOS), but the ovulatory response is variable, and the causes of this variation are poorly understood., Objective: Our objective was to identify predictive genetic polymorphisms and other determinants of ovulatory response., Design: This was a substudy of a multicenter randomized clinical trial., Setting: This study was performed at academic medical centers and their affiliates., Participants: A total of 312 women with PCOS were included in the study., Main Outcome Measures: Historical, biometric, biochemical, and genetic parameters were performed., Results: We found that the C allele of a single nucleotide polymorphism in the STK11 gene (expressed in liver; also known as LKB1) was associated with a significantly decreased chance of ovulation in PCOS women treated with metformin. In an analysis of ovulation per cycle, the adjusted odds ratio (OR) comparing the C/C genotype to the G/G genotype was 0.30 [95% confidence interval (CI) 0.14, 0.66], and the OR for the C/G genotype vs. the G/G genotype was also 0.30 (95% CI 0.14, 0.66). In an analysis of metformin-treated subjects, we found that the percentage of women who ovulated increased with the number of G alleles present: 48% (10 of 21) of C/C women, 67% (32 of 48) of C/G women, and 79% (15 of 19) of G/G women ovulated. We also found that increased frequency of ovulation was associated with lower body mass index (BMI) [adjusted OR of 2.36 (95% CI 1.65, 3.36) and 2.05 (95% CI 1.46, 2.88), respectively, for comparisons of BMI less than 30 vs. BMI equal to or more than 35, BMI 30-34 vs. BMI equal to or more than 35, in the analysis of ovulation per cycle], a lower free androgen index (FAI) [adjusted OR of 1.59 (95% CI 1.17, 2.18) for FAI<10 vs. FAI>or=10], and a shorter duration of attempting conception [adjusted OR of 1.63 (95% CI 1.20, 2.21) for<1.5 vs.>or=1.5 yr]., Conclusions: We have demonstrated that a polymorphism in STK11, a kinase gene expressed in liver and implicated in metformin action, is associated with ovulatory response to treatment with metformin alone in a prospective randomized trial. The interaction with the effects of changes in modifiable factors (e.g. BMI or FAI) requires further study.

Statin treatment markedly reduces the incidence of acute coronary events in patients with coronary atherosclerosis. Although imaging studies have indirectly shown the beneficial effects of statins on plaque morphology, there has to our knowledge been no reported histologic comparison of the morphology of coronary plaque in statin-treated versus untreated patients who had substantial coronary artery atherosclerosis. We retrospectively studied arterial sections from the native hearts of patients who had experienced end-stage ischemic heart disease and subsequent cardiac transplantation. Of 44 qualified patients, 33 study patients had received pre-transplantation statin therapy, and 11 control patients had not. Pathologic examination of each explanted heart confirmed coronary artery disease and previous myocardial infarction in all patients. Diabetes mellitus was more prevalent in the study group. The groups were similar in levels of total and low-density lipoprotein cholesterol, and in the available number of arterial cross-sections per patient. All patients had plaques. High-grade lesions were found in 66.3% of cross-sections in the control group, and in 34.6% in the study group (P=0.011). Conversely, the degree of inflammation was markedly lower in the study group: low-grade fibrous plaques occurred in 45.7% of cross-sections in the study group, versus 11.3% in the control group (P=0.006). The study group had significantly fewer high-grade plaques and more fibrous plaques than did the control group at the time of transplantation. Our findings show that statin therapy substantially enhances plaque stabilization. We further suggest that reduction of plaque inflammation is an important aspect of this stabilization.

We investigated the prevalence of abnormal screening results (questionnaire and testing for other causes of oligo-ovulation, male or tubal factor infertility) in a group of 1,313 oligo-ovulatory women (included and excluded subjects) whose condition was screened for inclusion in the Pregnancy in Polycystic Ovary Syndrome trial, a multicenter clinical trial that was conducted at 13 sites in the United States. Other than failure to demonstrate laboratory evidence of hyperandrogenemia, the most common reasons for subject exclusion were persistent oligospermia and tubal factor infertility.

Objective: To report the baseline characteristics and racial differences in the polycystic ovary syndrome (PCOS) phenotype from a large multicenter clinical trial (PPCOS)., Design: Double-blind, randomized trial of three treatment regimens (with extended release metformin or clomiphene citrate)., Setting: Academic medical centers., Patient(s): Six hundred twenty-six infertile women with PCOS, aged 18-39 years, with elevated T levels and oligomenorrhea (exclusion of secondary causes), seeking pregnancy, with > or = 1 patent fallopian tube, normal uterine cavity, and a partner with sperm concentration > or = 20 x 10(6)/mL in > or = 1 ejaculate., Intervention(s): Baseline characterization., Main Outcome Measure(s): Historical, biometric, and biochemical measures of PCOS., Result(s): There were no significant differences in baseline variables between treatment groups. The overall mean (+/-SD) age of the subjects was 28.1 +/- 4.0 years, and the mean body mass index was 35.2 kg/m2 (+/-8.7). Polycystic ovaries (PCOs) were present in 90.3% of the subjects, and the mean volume of each ovary was 10 cm3 or more. Of the subjects, 7% had ovaries that were discordant for PCO morphology. At baseline, 18.3% of the subjects had an abnormal fasting glucose level (> 100 mg/dL). Asians tended to have a milder phenotype, and whites and African Americans were similar in these measures., Conclusion(s): The treatment groups were well matched for baseline parameters, and we have added further information to the PCOS phenotype.

Objective: To determine if obstetric outcome is compromised in pregnancies in which a spontaneous pregnancy reduction (SPR) occurred in the first trimester., Study Design: Case-control study., Results: First-trimester SPR was diagnosed in 29 (27.8%) of 104 twin pregnancies, 14 (28.6%) of 49 triplet pregnancies and 10 (28.6%) of 35 quadruplet pregnancies. Of these 53 patients, 15 were excluded from the analysis. In the remaining 38 women with SPR, vaginal bleeding occurred in 2 (5.3%) as compared to 7 (8.3%) of the controls. Pregnancy-induced hypertension occurred in 4 (10.5%) of SPR pregnancies as compared to 9 (10.7%) of control pregnancies. When compared to respective controls, there were no significant differences in the birth weights or gestational age at delivery of pregnancies spontaneously reduced to singletons (SPR, 38.5 weeks; controls, 38.2 weeks), twins (SPR, 36.2 weeks; controls, 34.4 weeks) or triplets (SPR, 31.0 weeks; controls, 32.0 weeks)., Conclusion: SPR can be recognized in >25% of multiple pregnancies diagnosed in the early first trimester. Our data suggests that SPR is not associated with decreased gestational age at delivery, reduced birth weight or increased incidence of pregnancy-induced hypertension.

Objective: To assess the ability of histological dating to discriminate between women of fertile and infertile couples. The utility of histological dating of endometrium in the evaluation of infertile couples is uncertain., Design: Prospective multicenter study, with subjects randomly assigned to biopsy timing. Criterion standard for infertility was 12 months of unprotected, regular intercourse without conception and for fertility at least one live birth within 2 years., Setting: University-based infertility practices., Patient(s): Volunteer subjects (847) recruited at 12 clinical sites participating in the National Institutes of Health-funded Reproductive Medicine Network. Inclusion criteria included ages 20-39 years, regular menstrual cycles, and no hormonal treatment or contraceptive use for 1 month before the study. Fertile controls were excluded if they had a history of infertility, recurrent pregnancy loss, or recent breastfeeding., Intervention(s): Subjects underwent daily urinary LH testing. After detection of the LH surge, subjects were randomized to biopsy in the mid (days 21-22) or the late (days 26-27) luteal phase. Pathologists at each site estimated the cycle day based on standard criteria. For the primary analysis, an out-of-phase biopsy was defined as a greater than 2-day delay in the histological maturation of the endometrium., Main Outcome Measure(s): The proportion of out-of-phase biopsies in fertile and infertile women was compared using logistic regression models with age at randomization as a covariate. Comparisons were also made between fertile vs. infertile at the midluteal or late luteal phase time points., Result(s): Biopsies were evaluated (301 mid and 318 late; N = 619). Out-of-phase biopsy results poorly discriminated between women from fertile and infertile couples in either the midluteal (fertile: 49.4%, infertile: 43.2%) or late luteal phase (fertile: 35.3%, infertile 23.0%). Results did not substantially differ using alternative definitions of "out-of-phase" or standardized cycle day., Conclusion(s): Histological dating of the endometrium does not discriminate between women of fertile and infertile couples and should not be used in the routine evaluation of infertility.

Objective: To examine the proportion of cases with proliferative endometrium on biopsies performed after positive home urine LH testing., Design: Multicenter clinical trial of the usefulness of endometrial biopsy in the evaluation of infertility, with women from fertile and infertile couples randomly assigned to midluteal vs. late luteal phase endometrial sampling., Setting: Twelve clinical sites of the National Institutes of Health/National Institute of Child Health and Human Development-sponsored Reproductive Medicine Network., Patient(s): All women in the study had regular menstrual cycles. Fertile volunteers who had delivered a live born infant within the past 2 years without medical intervention were recruited through advertisements at participating sites. Infertile women with regular cycles were recruited from the clinical practices of the sites' physicians., Intervention(s): Interview, informed consent, subject-interpreted home urine LH testing, and endometrial biopsy in either the midluteal or late luteal phase., Main Outcome Measure(s): Proportion of cases with proliferative endometrium on biopsy., Result(s): In both fertile and infertile women, more than 7% of endometrial biopsies performed 7-13 days after a positive home urine LH test revealed proliferative endometrium., Conclusion(s): Patient interpretation of home urine LH test kits not uncommonly results in false-positive tests. Women planning menstrual cycle testing or procedures related to ovulation may benefit from additional confirmatory testing.

Objective: To report on a patient with thalidomide-induced amenorrhea and review the literature on the effect of thalidomide on ovarian function., Design: Case report and literature review., Setting: University medical center., Patient(s): A twenty-eight-year-old woman referred for a 2-year history of amenorrhea., Intervention(s): History, physical examination, laboratory evaluation of the patient, and subsequent medical therapy. Literature review performed by using OVID/Medline and PubMed search strategies., Main Outcome Measure(s): Diagnosis and appropriate management of thalidomide-induced amenorrhea., Result(s): Elevated pituitary gonadotropins, other labs normal. All known causes of hypergonadotropic amenorrhea were excluded., Conclusion(s): Thalidomide induces hypergonadotropic amenorrhea. Although this effect appears to be reversible, the long-term effect of thalidomide on ovarian reserve is unclear.

Objective: To present a case report of a patient with primary infertility from female circumcision, the management of the patient, and a review of the literature., Design: Case report and literature review., Setting: University hospital., Patient(s): A 31-year-old woman referred for a history of primary infertility., Intervention(s): Complete history and physical exam of the patient and subsequent deinfibulation., Main Outcome Measure(s): Diagnosis, surgical management, and postoperative sexual function and pregnancy., Result(s): Resolution of dyspareunia, satisfactory postoperative sexual function, and pregnancy., Conclusion(s): Awareness of this type of female circumcision and familiarity with its surgical management may prevent delays and any subsequent complications.

Objective: To assess the value of laparoscopic evaluation of the pelvis after failure to achieve pregnancy with clomiphene citrate-induced ovulation and to determine whether predictors for significant pelvic pathology can be isolated., Design: Retrospective study., Setting: Tertiary care academic medical center., Patient(s): Ninety-two patients failing to conceive after four ovulatory cycles with clomiphene citrate with a normal hysterosalpingogram who underwent laparoscopic evaluation of the pelvis., Intervention(s): Laparoscopy., Main Outcome Measure(s): Presence of pelvic pathology and predictors of pelvic disease., Result(s): Of the 92 patients studied, 32 patients (34.8%) had a "positive" laparoscopy (i.e., stages III and IV endometriosis, an endometrioma, pelvic adhesions, and/or tubal disease), 27 patients (29.3%) had stage I or II endometriosis, and 30 patients (32.6%) had a normal pelvis. The predictors for intrapelvic disease were a history of dyspareunia, no prior use of oral contraceptive pills, and no prior use of any form of contraception. Almost 40% of women with predictors had a "positive" laparoscopy, compared with only 12.5% of patients without predictors; however, the majority of patients (91.3%) had at least one predictor., Conclusion(s): More than one third of the patients failing to conceive after four ovulatory cycles of clomiphene citrate had significant intrapelvic pathology. Although predictors for intrapelvic disease were isolated, their high prevalence reduced their predictive value.

Objective: To determine the outcome of women with early-stage ovarian malignancies who subsequently underwent assisted reproductive technologies (ART)., Design: Retrospective study., Setting: Academic assisted reproductive technology program., Patient(s): Four infertile women who were previously diagnosed with early-stage ovarian malignancies., Intervention(s): Controlled ovulation hyperstimulation, IVF, and/or gamete intrafallopian transfer treatments using clomiphene citrate and/or gonadotropins., Main Outcome Measure(s): Development of tumor recurrence and disease-free interval., Result(s): All four women remain free of disease for up to 15 years after treatment. Three of the four women achieved pregnancy., Conclusion(s): In patients with early-stage ovarian malignancies, conservative therapy followed by ovarian stimulation for assisted reproduction is an acceptable strategy.

Objective: The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/d) in either the first (protocol A) or last (protocol B) 12-week period as well as a 6-month course of the GnRH agonist (GnRH-a; leuprolide acetate; 1 mg/d, SC) on calcium (Ca) metabolism., Design: Prospective, randomized, double-blind, placebo-controlled, crossover trial., Setting: Clinical research center, university hospital., Patient(s): Twenty women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, and were then crossed over at 12 weeks to placebo or MPA, for the final 12-week interval of GnRH-a therapy., Intervention(s): Collection of serum and urine samples and measurement of bone density. Sex hormone, calcitropic hormone, and bone density studies were performed at baseline and at 12 and 24 weeks., Result(s): In both protocol A and B, LH and E(2) levels declined by 79%-81% and 83%-90% of the baseline, respectively, at 12 and 24 weeks. Serum Ca, phosphorus, alkaline phosphatase, and osteocalcin; 2-h fasting and 24-h urinary Ca excretion; and urinary hydroxyproline levels all increased significantly during GnRH-a treatment alone. Estimated Ca balance decreased significantly during GnRH-a treatment alone. The addition of MPA attenuated the increases in phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion, and the decrease in estimated Ca balance. Comparison of phase order demonstrated that MPA prevented 24-h urinary Ca excretion and urinary hydroxyproline loss and decline in estimated Ca balance when it was added back during the second 12 weeks (protocol B) but not during the first 12 weeks (protocol A). CONCLUSION (S): We conclude that sequential MPA appears to reverse in part the negative effects of GnRH-a on calcitropic hormones and estimated Ca balance.

Background: These data compare the efficacy and safety of highly purified human-derived follicle-stimulating hormone (Bravelle) and recombinant follitropin-beta (Follistim) in women undergoing in vitro fertilization., Methods: This report describes the pooled data from two, nearly identical, randomized, controlled, parallel-group, multicenter studies conducted in a total of 19 academic and private IVF-ET centers in the United States. Infertile premenopausal women underwent pituitary down-regulation using leuprolide acetate followed by a maximum of 12 days of subcutaneous Bravelle (n = 120) or Follistim (n = 118), followed by administration of human chorionic gonadotropin, oocyte retrieval and embryo transfer. The primary efficacy measure was the mean number of oocytes retrieved; secondary efficacy measures included the total dose and duration of gonadotropin treatment; peak serum estradion levels; embryo transfer and implantation rates; chemical, clinical and continuing pregnancies; and live birth rates. All adverse events were recorded and injection site pain was recorded daily using a patient, self-assessment diary., Results: Similar efficacy responses were observed for all outcome parameters in the two treatment groups. Although patients receiving Bravelle consistently reported a greater number of chemical, clinical and continuing pregnancies, as well as an increased rate of live birth, the data did not attain statistical significance (P > 0.05). The overall incidence of adverse events was similar in both groups, but compared to Follistim, injections of Bravelle were reported by patients to be significantly less painful (P < 0.001)., Conclusions: Bravelle and Follistim had comparable efficacy in controlled ovarian hyperstimulation in women undergoing IVF-ET. There were no differences in the nature or number of adverse events between the treatment groups although Bravelle injections were reported to be significantly less painful.

Objective: To report the first case of monozygotic twins with discordant congenital anomalies., Design: Descriptive case report., Setting: University hospital., Patient(s): A 20-year woman with complete vaginal agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome) and right renal agenesis presented for creation of a neovagina. She had a monozygous twin confirmed by DNA testing using short tandem repeat (STR) loci; the twin had normal mullerian/mesonephric development but isolated bilateral tibial longitudinal deficiency., Intervention(s): The complete history, physical, and laboratory data of both the patient and her twin. Also, operative laparoscopy with creation of a neovagina in the patient., Main Outcome Measure(s): Diagnosis and appropriate treatment of Mayer-Rokitansky-Kuster-Hauser syndrome and DNA testing with STR loci for monozygosity., Result(s): The surgical resection of the bilateral uterine remnants, creation of a neovagina in the patient, and the demonstration of monozygosity with her twin with bilateral tibial longitudinal deficiency., Conclusion(s): This case report suggests a link between developmental abnormalities of the genital and skeletal system.

Objective: To determine whether recombinant follicle-stimulating hormone (rFSH) should be administered intramuscularly (i.m.) or subcutaneously (s.c.) to obese women., Design: Randomized, single-center, two-way crossover study., Setting: Academic clinical research center., Subject(s): Nineteen healthy women of reproductive age with body mass indices of 19.9 kg/m(2)-42.8 kg/m(2)., Intervention(s): Leuprolide acetate 3.75 mg i.m. to achieve pituitary down-regulation as determined by serum E(2) levels. Subjects were then given a single dose of 300 IU rFSH either i.m. or s.c.. Multiple blood sampling was performed over the next two weeks, and after retreatment with leuprolide, a second 300 IU rFSH dose was given via the other administration route., Main Outcome Measure(s): Serum samples were analyzed in duplicate for follicle-stimulating hormone (FSH) using a standard radioimmunoassay in a single run. Maximum concentrations (C(max)), times to C(max) (T(max)), and extent of absorption (area under curve [AUC]) with i.m. vs. s.c. administration were compared using paired analysis., Result(s): Maximal concentrations were achieved within 24 hours with both s.c. and i.m. routes. No significant differences were found in C(max), T(max), or AUC with s.c. vs. i.m. administration. A decline of AUC occurred among subjects of higher body mass index (BMI) with rFSH given either s.c. or i.m.. Subcutaneous administration achieved AUCs comparable to i.m. administration in both normal-weight and obese subjects., Conclusion(s): Our data indicate that the s.c. administration of rFSH is appropriate for women regardless of body mass.

Objective: To report on a one-year experience participating in a capitated healthcare plan for infertility., Design: Prospective study., Setting: University population., Patient(s): Reproductive-age women 15 to 50 years., Intervention(s): The first-generation Lewin infertility algorithm and CATHI software were used to negotiate infertility services under a capitated arrangement for $0.50 per member per month. The following reports our experience for the fiscal year 1997., Main Outcome Measure(s): Infertility services rendered, pregnancy rate, cost of services, collection rates., Result(s): Five thousand forty-six women representing 39,689 member months generated 39 new and 198 return visits. Thirty-two percent of the patients required three visits or less; six patients generated 22% of the visits. Fifty-one percent listed infertility as one of their chief complaints; 31% had mixed diagnoses. Eight (7.6%) patients required surgery, 11 (10.5%) patients underwent either IVF or GIFT cycles. Total charges submitted were $176,636; the amount assigned to specialty care was $135,277, and to IVF/GIFT, $33,433. Total capitated payments, including copayments, was $126,256 under the reproductive medicine agreement and $32,891 under the infertility rider. This resulted in a 71% gross collections rate., Conclusion(s): This study indicates that entering into a capitated health care plan to provide an infertility benefit can produce a successful result.

Background: Whether anesthetic agents administered during gamete intrafallopian transfer (GIFT) affect reproductive outcome is controversial. This multicenter pilot trial and survey had two purposes: to evaluate the effect of propofol, nitrous oxide, midazolam, and isoflurane on pregnancy outcome after GIFT, and to determine if a larger prospective, randomized study is warranted., Methods: A written invitation was mailed to all 50 fertility programs in the United States that are members of the Society for Assisted Reproductive Technology and perform more than 30 GIFT procedures per year. They were invited to contribute information from the medical records of women who underwent GIFT during the calendar years 1993 and 1994. They were asked to document whether propofol, nitrous oxide, midazolam, a potent inhaled anesthetic agent was used during the GIFT procedure; if the woman became pregnant; and if she delivered at least one live neonate., Results: Seven medical centers participated and contributed data from 455 women. The clinical pregnancy rate (number of pregnancies/total number of GIFT procedures) and the delivery rate (number of women who delivered at least one live baby/total number of GIFT procedures) were 35% and 32%, respectively. A statistically significant difference could not be found in the clinical pregnancy or delivery rates between those women who received propofol, nitrous oxide, midazolam, or isoflurane during GIFT and those who did not., Conclusions: No agent-related differences in pregnancy rates were found when propofol, nitrous oxide, isoflurane, or midazolam was used as part of the anesthetic technique for GIFT. Therefore, a more extensive prospective trial does not appear to be warranted.

Objective: To analyze the efficacy and cost-effectiveness of alternative treatments for unexplained infertility., Design: Retrospective analysis of 45 published reports., Setting: Clinical practices., Patient(s): Couples who met criteria for unexplained infertility. Women with Stage I or Stage II endometriosis were included., Intervention(s): Observation; clomiphene citrate (CC); gonadotropins (hMG); IUI; and GIFT and IVF., Main Outcome Measure(s): Clinical pregnancy rate., Result(s): Combined pregnancy rates per initiated cycle, adjusted for study quality, were as follows: no treatment = 1.3%-4.1%; IUI = 3.8%; CC = 5.6%; CC + IUI = 8.3%; hMG = 7.7%; hMG + IUI = 17.1%; IVF = 20.7%; GIFT = 27.0%. The estimated cost per pregnancy was $10,000 for CC + IUI, $17,000 for hMG + IUI, and $50,000 for IVF., Conclusion(s): Clomiphene citrate + IUI is a cost-effective treatment for unexplained infertility. If this treatment fails, hMG + IUI and assisted reproduction are efficacious therapeutic options.

Background: The optimal treatment of infertility due to tubal occlusion has not been established. Many practitioners feel that the success of tubal repair exceeds that of in vitro fertilization (IVF); however, previous studies of pregnancy after tubal surgery have been limited by bias in patient selection, follow-up, or surgical expertise. The purpose of the present study was to determine the outcome after repair of distal tubal occlusion performed by experienced surgeons in an unselected patient population with consistent follow-up.Design: Chart review with telephone contact of patients lost to follow-up.Methods: The records of all tubal surgery performed between 1989 and 1996 at the University of Alabama Hospital and The Kirklin Clinic outpatient surgery facility were reviewed. All women with infertility due to distal tubal occlusion, with or without pelvic adhesions, who had no other significant infertility factors were included for study. Details of the infertility history, operative procedure, and postoperative course were recorded. Patients lost to follow-up within 1 year after surgery were contacted by telephone for information regarding subsequent testing and treatment and pregnancy outcome.Results: Eighty-three women aged 19-39 years met the entry criteria for this study. Follow-up of at least 1 year was obtained in all but 11 patients. Tubal surgery was accomplished by laparotomy in 19 women; 64 women underwent tubal repair by laparoscopy. Within 1 year of surgery, 9 hysterosalpingograms, 51 clomiphene cycles, and 20 gonadotropin cycles were performed on the study group. Pregnancy was achieved within 1 year in 13 women; of these, there were 6 live births (9.6% birth rate per surgery), 2 spontaneous abortions, and 3 ectopic pregnancies. There were no live births among women who underwent tubal repair by laparotomy. None of the postoperative gonadotropin cycles resulted in pregnancy. Seven women underwent IVF within 1 year after surgery because of extensive tubal damage noted at surgery. Based on current charges for the infertility treatments performed, the cost of a live birth with tubal surgery exceeded $120,000, versus less than $50,000 per live birth with IVF using results obtained nationally or at UAB.Conclusions: The cost-effectiveness of reconstructive surgery in unselected patients with distal tubal occlusion is less than that of IVF. Empiric use of gonadotropins for ovarian stimulation does not improve pregnancy rates after tubal surgery. In our series, laparoscopic tubal repair seemed to give results superior to that of laparotomy.

Objective: To assess the feasibility of logistic regression analysis for determining the gestational ages at which detection of early pregnancy landmarks first can be observed., Design: Retrospective analysis., Setting: University-based tertiary care clinic., Patient(s): Eighty-two women with viable singleton pregnancies in whom ovulation had been achieved by an injection of hCG., Intervention(s): Two hundred fifteen transvaginal sonographic scans., Main Outcome Measure(s): Logistic regression was used to estimate the probability of detection of sonographic findings as a function of gestational age., Result(s): We found that the likelihood of visualization of a gestational sac or fetal heart motion could be represented accurately by logistic equations. Gestational age at which there was 95% probability of visualization was 35.5 days for the gestational sac and 44.5 days for fetal cardiac activity. The probability of detecting fetal cardiac activity was 95% when the mean gestational sac diameter was 1.6 cm and was 99% at 1.9 cm., Conclusion(s): The sonographic appearances of developmental landmarks in early pregnancy occurs within well-defined gestational time periods, and the probabilities for visualization can be closely approximated using a logistic model. Our results suggest that the number of sonographic examinations required to document infertility treatment success can be minimized by surveillance at standardized gestational ages.

Objective: To evaluate the effect of a routine breast examination on serum PRL levels., Design: Prospective clinical study., Setting: University-based reproductive endocrinology unit., Patients: Eleven nonlactating, euprolactinemic women of reproductive age with a history of regular menstrual cycles and currently taking no medications., Interventions: Breast examination using standard technique., Main Outcome Measure: Changes in serum PRL levels after breast examination., Results: Baseline PRL levels ranged from 3.64 to 19.23 ng/mL (mean 7.17 ng/mL; conversion factor to SI unit, 1.00). There were no significant increases in PRL levels after breast examination, with mean PRL levels after 15, 30, and 45 minutes of 6.59, 6.84, and 6.45 ng/mL, respectively., Conclusion: Routine breast examination does not alter acutely serum PRL levels in normal women.

Objective: To compare the obstetric outcomes of twin pregnancies obtained as a result of multifetal pregnancy reduction to those in which pregnancy reduction had not been used., Design: Retrospective analysis., Setting: University-based tertiary care infertility clinic., Patients: Seventy-four twin pregnancies continuing beyond 10 weeks. Of these, 32 gestations had undergone reduction to twins at 10 weeks., Main Outcome Measures: Gestational age at delivery, birth weights, pregnancy complications., Results: All pregnancies advanced beyond 20 weeks gestation. The mean gestational age at delivery of the reduction group was 33.8 versus 35.7 weeks in the nonreduced group; only 25% of reduced pregnancies reached 37 weeks compared with 57.9% of nonreduced twins. The mean fetal birth weights of the two groups differed significantly (reduced: 2,038 g, nonreduced: 2512 g). The gestational age at delivery in patients reduced from triplets was significantly greater than in pregnancies reduced from quadruplets or higher. Multiple regression analysis revealed that for a given gestational age at delivery, a history of pregnancy reduction was associated with decreased birth weight., Conclusion: These data suggest that multifetal pregnancy reduction does not reverse completely the decreased gestational age and impaired fetal growth associated with high-order multiple pregnancy. Furthermore, fetal growth of reduced pregnancies seems to be impaired independent of the gestational age at which delivery occurs.