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STUDY QUESTION Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate in patients with recurrent pregnancy loss (RPL)? SUMMARY ANSWER PGT-A use was associated with improved live birth rates in couples with recurrent pregnancy loss undergoing frozen embryo transfer (IVF-FET). WHAT IS KNOWN ALREADY Euploid embryo transfer is thought to optimize outcomes in some couples with infertility. There is insufficient evidence, however, supporting this approach to management of recurrent pregnancy loss. STUDY DESIGN, SIZE, DURATION This study included data collected by the Society of Assisted Reproductive Technologies Clinical Outcomes Reporting System (SART-CORS) for IVF-FET cycles between years 2010 through 2016. A total of 12 631 FET cycles in 10 060 couples were included in this analysis designed to assess the utility of PGT-A in couples with RPL undergoing FET, including 4287 cycles in couples with tubal disease who formed a control group. PARTICIPANTS/MATERIALS, SETTING, METHODS The experimental group included couples with RPL (strictly defined as a history of 3 or more pregnancy losses) undergoing FET with or without PGT-A. The primary outcome was live birth rate. Secondary outcomes included rates of clinical pregnancy, spontaneous abortion, and biochemical pregnancy loss. Differences were analyzed using generalized estimating equations logistic regression models to account for multiple cycles per patient. Covariates included in the model were age, gravidity, geographic region, race/ethnicity, smoking history, and indication for assisted reproductive technologies. Analyses were stratified for age groups as defined by SART: 42 years. MAIN RESULTS AND THE ROLE OF CHANCE In women with a diagnosis of RPL, the adjusted odds ratio (OR) comparing IVF-FET with PGT-A versus without PGT-A for live birth outcome was 1.31 (95% CI: 1.12, 1.52) for age 42 years. For clinical pregnancy, the OR was 1.26 (95% CI: 1.08, 1.48) for age 42 years. Finally, for spontaneous abortion, the OR was 0.95 (95% CI: 0.74, 1.21) for age 42 years. LIMITATIONS, REASONS FOR CAUTION The retrospective collection of data including only women with recurrent pregnancy loss undergoing FET presents a limitation of this study, and results may not be generalizable to all couples with recurrent pregnancy loss. Also, data regarding evaluation and treatment for RPL for the included women is unavailable. WIDER IMPLICATIONS OF THE FINDINGS This is the largest study to date assessing the utility of PGT-A in women with RPL. PGT-A was associated with improvement in live birth and clinical pregnancy in women with RPL, with the largest difference noted in the group of women with age greater than 42 years. Couples with RPL warrant counseling on all management options to reduce subsequent miscarriage, which may include IVF with PGT-A for euploid embryo selection. STUDY FUNDING/COMPETING INTEREST(S) There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

Objective This study aims to determine whether myometrial artery calcifications increase with age and whether uterine sections are an appropriate model for studying vascular aging. Methods An observational study of 172 women (aged 45 y or older) who underwent hysterectomy for benign indications at the University Hospital (Newark, NJ) between July 1, 2009 and June 1, 2012 was performed. Women with a history of malignancy, undocumented last menstrual period, or unavailable uterine tissue slides were excluded. H&E-stained uterine sections were evaluated for myometrial artery calcifications (defined as the presence of acellular densely basophilic material within the media of vessels) by a single pathologist in a blinded manner. Results Between July 1, 2009 and June 1, 2012, hysterectomies were performed on 441 women, 172 of whom met inclusion criteria. Seventeen women (9.9%) had myometrial artery calcifications detectable on H&E-stained tissue sections. None of 84 women aged 45 to 49 years, 2 of 51 women (3.9%) aged 50 to 59 years (aged 56 and 58 y), 10 of 27 women (37%) aged 60 to 69 years, and 5 of 10 women (50%) aged 70 to 81 years had myometrial artery calcifications. The prevalence of myometrial artery calcifications significantly increased with advancing age (P = 0.022). Conclusions Myometrial artery calcifications increase with advancing age. Histological sections of uterine tissue from hysterectomy specimens seem to be a useful model for evaluating vascular aging markers.

Objective To investigate whether there is a difference in obstetrical and perinatal outcomes in blastocyst frozen-thawed embryo transfers (FETs) compared with cleavage-stage FET. Design A retrospective cohort study. Setting Not applicable. Patient(s) Women undergoing autologous FETs at either the blastocyst stage (n = 118,572) or the cleavage stage (n = 117,619) reported to the Society for Assisted Reproductive Technology in the years 2004–2013. Intervention(s) None. Main Outcome Measure(s) Live birth, gestational age, birth weight, miscarriage. Result(s) After controlling for confounders, there were a 49% increased odds of live birth after blastocyst-stage FET compared with cleavage-stage FET (odds ratio [OR] = 1.49; 95% confidence interval [CI], 1.44, 1.54). Additionally, blastocyst FET was associated with a 68% (OR = 1.68; 95% CI, 1.63, 1.74) increased odds of clinical pregnancy and an 7% (OR = 0.93; 95% CI, 0.88, 0.92) decreased odds of miscarriage. There was also a 16% increased odds of preterm delivery (OR = 1.16; 95% CI, 1.06, 1.27) after blastocyst FET but no difference in birth weights. Conclusion(s) In patients undergoing FET, blastocyst-stage transfer is associated with higher live-birth rates when compared with cleavage-stage transfers. Furthermore, perinatal outcomes are similar between the groups.

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

Women with polycystic ovary syndrome have substantially higher rates of insulin resistance, impaired glucose tolerance, type 2 diabetes, dyslipidemia, and metabolic syndrome when compared with women without the disease. Given the high prevalence of these comorbidities, guidelines issued by the American College of Obstetricians and Gynecologists and the Endocrine Society recommend that all women with polycystic ovary syndrome undergo screening for impaired glucose tolerance and dyslipidemia with a 2 hour 75 g oral glucose tolerance test and fasting lipid profile upon diagnosis and also undergo repeat screening every 2-5 years and every 2 years, respectively. Although a hemoglobin A1C and/or fasting glucose are widely used screening tests for diabetes, both the American College of Obstetricians and Gynecologists and the Endocrine Society preferentially recommend the 2 hour oral glucose tolerance test in women with polycystic ovary syndrome as a superior indicator of impaired glucose tolerance/diabetes mellitus. However, we found that gynecologists underutilize current recommendations for metabolic screening in women with polycystic ovary syndrome. In an online survey study targeting American College of Obstetricians and Gynecologists fellows and junior fellows, 22.3% of respondents would not order any screening test at the initial visit for at least 50% of their patients with polycystic ovary syndrome. The most common tests used to screen for impaired glucose tolerance in women with polycystic ovary syndrome were hemoglobin A1C (51.0%) and fasting glucose (42.7%). Whereas 54.1% would order a fasting lipid profile in at least 50% of their polycystic ovary syndrome patients, only 7% of respondents order a 2 hour oral glucose tolerance test. We therefore call for increased efforts to encourage obstetrician-gynecologists to address metabolic abnormalities in their patients with polycystic ovary syndrome. Such efforts should include education of physicians early in their careers, at the medical student and resident level. Efforts should also include implementation of continuing medical education activities, both locally and at the national level, to improve understanding of the metabolic implications of polycystic ovary syndrome. Electronic medical record systems should be utilized to generate prompts for appropriate screening tests in patients with a diagnosis of polycystic ovary syndrome. Because obstetrician-gynecologists may be the only physicians seen by many polycystic ovary syndrome patients, particularly those in their young reproductive years, such interventions could effectively promote optimal preventative health care and early diagnosis of metabolic comorbidities in these at-risk women.

Experimental evidence supports a relevance of vitamin D (VitD) for reproduction; however, data in humans are sparse and inconsistent.To assess the relationship of VitD status with ovulation induction (OI) outcomes in women with polycystic ovary syndrome (PCOS).A retrospective cohort.Secondary analysis of randomized controlled trial data.Participants in the Pregnancy in PCOS I (PPCOS I) randomized controlled trial (n = 540) met the National Institutes of Health diagnostic criteria for PCOS.Serum 25OHD levels were measured in stored sera.Primary, live birth (LB); secondary, ovulation and pregnancy loss after OI.Likelihood for LB was reduced by 44% for women if the 25OHD level was30 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.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.

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.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.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.In infertile hirsute women with PCOS, treatment with clomiphene citrate, metformin, or both for up to six cycles does not alter hirsutism.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00068861.II.

Since the first description of successful human in vitro fertilization in 1978, researchers and clinicians have been striving to improve the efficacy and safety of the technique. Advances in technology and in our understanding of human reproduction have contributed to increased success rates and decreased rates of higher order multiple births. However, there is still room for improvement as 'unexplained infertility' still affects many couples, and the incidence of twin pregnancies remains elevated. This review will discuss some of the recent advances in the fields of molecular genetics, proteomics and oocyte culture that will ultimately enhance the clinical practice of preimplantation genetic diagnosis, embryo selection and in vitro maturation. It will also discuss the potential for these advances to improve both the safety and efficacy of in vitro fertilization in the near future.

Objective To describe fertility patients' preferences for disposition of cryopreserved embryos and determine factors important to these preferences. Design Cross-sectional survey conducted between June 2006 and July 2007. Setting Nine geographically diverse U.S. fertility clinics. Patient(s) 1020 fertility patients with cryopreserved embryos. Intervention(s) Self-administered questionnaire. Main Outcome Measure(s) Likelihood of selecting each of five conventional embryo disposition options: store for reproduction, thaw and discard, donate to another couple, freeze indefinitely, and donate for research; likelihood of selecting each of two alternative options identified in previous research: placement of embryos in the woman's body at an infertile time, or a disposal ceremony; importance of each of 26 considerations to disposition decisions; and views on the embryo's moral status. Result(s) We found that 54% of respondents with cryopreserved embryos were very likely to use them for reproduction, 21% were very likely to donate for research, 7% or fewer were very likely to choose any other option. Respondents who ascribed high importance to concerns about the health or well-being of the embryo, fetus, or future child were more likely to thaw and discard embryos or freeze them indefinitely. Conclusion(s) Fertility patients frequently prefer disposition options that are not available to them or find the available options unacceptable. Restructuring and standardizing the informed consent process and ensuring availability of all disposition options may benefit patients, facilitate disposition decisions, and address problems of long-term storage.

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).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.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.Study volunteers at multiple academic medical centers were included.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.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.Ovulation was confirmed by a serum progesterone more than or equal to 5 ng/ml, drawn prospectively every 1-2 wk.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.Metformin XR does not reduce the lowest dose of clomiphene that induces ovulation in women with PCOS.

Ovarian reserve tests are an indirect measurement of a woman's remaining follicular pool and give an estimate of her sensitivity to ovarian stimulation and her prognosis for success with fertility treatments. They cannot be used to predict future fertility or the exact timing of the decline or cessation of fertility. It is important to become familiar with these tests and understand their correct performance and interpretation, including their limitations. We review the correct timing and interpretation of the most commonly accepted tests of ovarian reserve, and suggest which patient populations will benefit most from screening. Discussed in detail are the natural age-related decline in fecundity, basal follicle stimulating hormone and estradiol levels, the clomiphene citrate challenge test, and use of transvaginal ultrasound for antral follicle counts. Other tests, such as for ovarian volume, anti-Müllerian hormone, gonadotropin-releasing hormone agonist and exogenous follicle-stimulating hormone, are discussed briefly.

Kallmann syndrome is a genetic disorder with the hallmarks of anosmia and hypogonadotrophic hypogonadism. It has a male preponderance. With the elucidation of the genetic pathways involved, affected females and inheritance patterns are becoming more clearly identified. It is an eminently treatable disorder, but it must first be recognized by the physician. With treatment, favorable reproductive outcomes can be attained in addition to maturation of secondary sex characteristics.

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 ≥ 10], and a shorter duration of attempting conception [adjusted OR of 1.63 (95% CI 1.20, 2.21) for < 1.5 vs. ≥ 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.

In this article we review the existing fertility preservation options for women diagnosed with Turner syndrome and provide practical guidelines for the practitioner. Turner syndrome is the most common sex chromosome abnormality in women, occurring in approximately 1 in 2500 live births. Women with Turner syndrome are at extremely high risk for primary ovarian insufficiency and infertility. Although approximately 70%-80% have no spontaneous pubertal development and 90% experience primary amenorrhea, the remainder might possess a small residual of ovarian follicles at birth or early childhood. The present challenge is to identify these women as early in life as is possible, to allow them to benefit from a variety of existing fertility preservation options. To maximize the benefits of fertility preservation, all women with Turner syndrome should be evaluated by an expert as soon as possible in childhood because the vast majority will have their ovarian reserve depleted before adulthood. Cryopreservation of mature oocytes and embryos is a proven fertility preservation approach, and cryopreservation of ovarian tissue is a promising technique with a growing number of live births, but remains investigational. Oocyte cryopreservation has been performed in children with Turner syndrome as young as 13 years of age and ovarian tissue cryopreservation in affected prepubertal children. However, current efficacy of these approaches is unknown in this cohort. For those who have already lost their ovarian reserve, oocyte or embryo donation and adoption are strategies that allow fulfillment of the desire for parenting. For those with Turner syndrome-related cardiac contraindications to pregnancy, use of gestational surrogacy allows the possibility of biological parenting using their own oocytes. Alternatively, gestational surrogacy can serve to carry pregnancy resulting from the use of donor oocytes or embryos, if needed.

OBJECTIVE: To estimate the effects of estrogen plus progestin (E+P) therapy on menopausal symptoms, vaginal bleeding, gynecologic surgery rates, and treatment-related adverse effects in postmenopausal women. METHODS: Randomized, double-blind, placebo-controlled trial of 16,608 postmenopausal women, ages 50-79 (mean +/- standard deviation 63.3 +/- 7.1) years, with intact uterus, randomized to one tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and followed for a mean of 5.6 years. Change in symptoms and treatment-related effects were analyzed at year 1 in all participants. Bleeding and gynecologic surgery rates were analyzed through study close-out. RESULTS: Baseline symptoms did not differ between the treatment groups. More women assigned to E+P than placebo reported relief of hot flushes (85.7% versus 57.7%, respectively; odds ratio 4.40; 95% confidence interval 3.40-5.71), night sweats (77.6% versus 57.4%; 2.58; 2.04-3.26), vaginal or genital dryness (74.1% versus 54.6%; 2.40; 1.90-3.02), joint pain or stiffness (47.1% versus 38.4%; 1.43; 1.24-1.64), and general aches or pains (49.3% versus 43.7%; 1.25; 1.08-1.44). Women asymptomatic at baseline who were assigned to E+P more often developed breast tenderness (9.3% versus 2.4%, respectively; 4.26; 3.59-5.04), vaginal or genital discharge (4.1% versus 1.0%; 4.47; 3.44-5.81), vaginal or genital irritation (4.2% versus 2.8%; 1.52; 1.27-1.81), and headaches (5.8% versus 4.7%; 1.26; 1.08-1.46) than women on placebo. Estrogen plus progestin treatment prevented the onset of new musculoskeletal symptoms. Vaginal bleeding was reported by 51% of women on E+P and 5% of women on placebo at 6 months; most bleeding was reported as spotting. Gynecologic surgeries (hysterectomy and dilation and curettage) were performed more frequently in women assigned to E+P (3.1% versus 2.5% for hysterectomy, hazard ratio = 1.23, P = .026; 5.4% versus 2.4% for dilation and curettage, hazard ratio = 2.23, P < .001). CONCLUSION: Estrogen plus progestin relieved some menopausal symptoms, such as vasomotor symptoms and vaginal or genital dryness, but contributed to treatment-related effects, such as bleeding, breast tenderness, and an increased likelihood of gynecologic surgery.

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.

The association of hysterectomy with increased coronary risk is controversial, and previous studies have reached differing conclusions as to whether the excess risk is confined to women who have also undergone bilateral oophorectomy. This analysis uses the Framingham algorithm to evaluate the hypothesis that hysterectomy with or without ovarian preservation is associated with increased coronary risk, using a cross-sectional analysis of baseline data from 1,501 participants of the Women's Health Initiative. Framingham risk scores, derived from the algorithm in the National Cholesterol Education Program Adult Treatment Panel III guidelines, which include age, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol, were determined in a subgroup of Women's Health Initiative participants with measured plasma lipids and known ovariectomy status. Women with hysterectomy had fewer years of education than those without hysterectomy (30% with college degree vs 41%, p0.0001) and higher body mass index (29 vs 28 kg/m(2), p0.0001), consumed less alcohol, exercised less, and had a higher Framingham risk of myocardial infarction or coronary death (46% vs 41% with 10-year risk/=4%, p = 0.04). In multivariate analysis, hysterectomy with bilateral oophorectomy was an independent predictor of Framingham risk (p = 0.04), whereas hysterectomy with ovarian preservation was not.

Objective: To test the hypothesis that our inner city obstetric patients who have been infected with sexually transmitted diseases (STDs) will have a higher prevalence of hepatitis C virus infection than the general population and to identify specific risk factors and high-risk groups. Methods: All patients in our prenatal clinic (July 1997–April 1999) who tested positive for one or more STDs were asked to return for hepatitis C antibody testing. Medical charts of all patients who returned for hepatitis C testing were reviewed. Results: A total of 106 patients with STDs were tested for hepatitis C. Positive screening tests for anti-hepatitis C antibody were found in 6.6% (7/106) of the patients (95% CI = 2.7–13.1%). This frequency is significantly higher than the hepatitis C prevalence (1.8%) in the general United States population (p = 0.006). Multiple logistic regression analysis confirmed only older age (p = 0.016) and positive HIV status (p = 0.023) to be significant predictors of hepatitis C infection. Conclusions: Inner city STD-infected obstetric patients are at high risk for hepatitis C infection compared with the general population. Increasing age and HIV-positive status are risk factors which are significantly associated with hepatitis C infection. Infection with the hepatitis C virus is the most common blood-borne infection in America. The prevalence in the general United States population is 1.8%. It is estimated that over 3.9 million Americans are currently infected and that 95% of these individuals are unaware of their infection 1 . About 75% of acute hepatitis C infections are asymptomatic; 80% of these patients will go on to have chronic infection 1 . Of patients with chronic infection, 25% will develop cirrhosis and 20% will progress to hepatocellular carcinoma in an average of 25 years 1 . Therefore, early identification of hepatitis C infection is important in

To determine whether elective single embryo transfer (eSET) reduces the risk of preterm delivery associated with in vitro fertilization (IVF).This is an observational study of 3125 eSET cycles performed from 2008 to 2009 and reported to the Society for Assisted Reproductive Technology (SART) database. Preterm delivery rates were compared to the overall preterm delivery rate among all patients undergoing IVF over the same time period.The 3125 eSET cycles resulted in 1507 live births (live birth rate 48.2 %) Among these deliveries were 27 twins (1.8 %) and one set of triplets (0.07 %). The overall preterm delivery rate (20-37 weeks gestation) following eSET was 17.6 % (269/1527). This is significantly greater than the preterm birth rate for all patients undergoing IVF over the same time period (12 %, P 0.001).Elective single embryo transfer does not reduce the risk of preterm delivery associated with in vitro fertilization (IVF).

Objective To test the hypothesis that the blastulation rate is higher in euploid embryos than in aneuploid embryos as assessed by cleavage-stage biopsy with array-comprehensive genomic hybridization (aCGH). Design Retrospective cohort study. Setting University-affiliated institution. Patient(s) Forty-one patients with 48 in vitro fertilization (IVF) cycles and 385 embryos that underwent cleavage-stage preimplantation genetic screening (PGS) with aCGH at the Continuum Reproductive Center between January 2010 and September 2013. Intervention(s) None. Main Outcome Measure(s) Probability of blastocyst and/or fully expanded or hatching blastocyst (FEHB) progression depending on number of chromosomal abnormalities. Result(s) Euploid embryos are twice as likely to progress to blastocyst and three times as likely to progress to FEHB than aneuploid embryos: 76% versus 37% and 56% versus 18%, respectively. For every additional chromosomal abnormality, the likelihood of progressing to the blastocyst stage decreases by 22% and the likelihood of progressing to FEHB decreases by 33%. Conclusion(s) Euploid embryos are far more likely than aneuploid embryos to progress to the blastocyst and FEHB stages. There is a linear decrease in probability of blastulation with the increasing number of chromosomal abnormalities.

In the first published demonstration that the antral follicle count (AFC) predicts live birth after in vitro fertilization-embryo transfer (IVF-ET), we found that an AFC ofor=11 was a strong positive predictor of live birth. The AFC should not be used to exclude women from IVF treatment; however, it is a very useful instrument for patient counseling and determining appropriate treatment protocols and gonadotropin dosing in IVF cycles.

Polycystic ovary syndrome (PCOS) may be the commonest cause of female infertility. In addition to anovulation, early pregnancy loss, and later complications of pregnancy, obesity-which is common in women with PCOS-has been implicated. Small-scale trials suggest that treatment with an insulin sensitizer such as metformin, alone or combined with clomiphene citrate, is at least equal to, and possibly superior to clomiphene alone as treatment for infertility. This randomized, placebo-controlled trial evaluated both of these agents, alone and combined, in 626 infertile women diagnosed as having PCOS. Extended-release metformin was given in a maximum dose of 1 gm daily, and clomiphene concurrently in a dose of 50 mg daily, starting on menstrual day 3. The dose of clomiphene was doubled if necessary. Treatment continued for up to six cycles over 30 weeks. Baseline variables were similar in all treatment groups. Rates of live birth were 22.5% in clomiphene-treated patients, 7.2% with metformin therapy, and 26.8% with combination therapy. The differences between the metformin group and the clomiphene and combined treatment groups were significant. Combined therapy was not significantly more effective than clomiphene alone. Similar results were obtained when adjusting for body mass index. Among secondary outcomes, ovulation rates were significantly higher with combined treatment than in either of the single-drug groups, but this did not translate into increased live births. Rates of conception and of live births per ovulatory cycle were significantly higher in the clomiphene and combined drug groups than with metformin alone. There were no multiple pregnancies in the metformin group. There were no notable group differences in rates of first-trimester pregnancy loss. Compared to metformin-treated women, those given clomiphene or combined therapy had significant increases in sex hormone-binding globulin levels and decreased free androgen indices. Serious adverse events-mostly pregnancy complications-were most frequent in the clomiphene and combined treatment groups. Gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms less frequent, in the metformin group than in the clomiphene group. These findings fail to support the view that extended-release metformin, alone or combined with clomiphene citrate, improves live birth rates in previously infertile women with PCOS. Clomiphene alone seems preferable as first-line treatment for these patients despite a risk of multiple births. Combining the two drugs does not further increase the chances of a live birth.

To assess the relationship between live birth rates (LBRs) and the incidence of under-reported cycles by IVF clinics.Cohort study.Not applicable.All patients undergoing IVF cycles in the aforementioned clinics.Not applicable.The reporting percentage (RP), defined as number of cycles with reported pregnancy rates divided by total cycles performed. Results from cryopreservation cycles are only presented by SART if an embryo transfer occurs. Thus, RP decreases as incidence of embryo or oocyte banking cycles increases. The LBRs in women aged35 years were compared between clinics.The median RP of all clinics was 93%-97%. Clinics with RP80% increased from 2 in 2004 to 30 in 2012. Twenty-one clinics had an RP that fell 2 standard deviations below the mean in any year. Over the 9 years, there was a negative correlation between RP and LBR of -0.17, but for the 21 outlier clinics the correlation increased to -0.26. In 2012 alone, in outlier clinics, for every 10% drop in RP there was an associated rise in LBR of 4.3%; some clinics reported 40% fewer cycles than the median.In clinics with very low RP, the cycles that are reported have higher success rates. Regardless of intent, the reduction of reported data to SART makes it increasingly difficult for clinicians and patients to accurately assess a clinic's success rates.

Background Recurrent acute episodes of pelvic inflammatory disease (PID) often present a diagnostic dilemma. The differential diagnosis should include reinfection, appendicitis, endometriosis, irritable bowel syndrome, colitis, persistent ovarian cyst, and antibiotic-resistant bacterial strains. Case A young Palestinian woman presented with recurrent episodes of pelvic pain with rebound tenderness, fever, and elevated white blood cell count, erythrocyte sedimentation rate, and C-reactive protein. The patient underwent extensive workup, multiple courses of intravenous and oral antibiotics, and diagnostic laparoscopies, with continued recurrent episodes. Treatment with colchicine for suspected familial Mediterranean fever resulted in resolution of symptoms. Conclusion In patients of Mediterranean ancestry who have symptoms of recurrent PID that are refractory to conventional treatment, familial Mediterranean fever should be included in the differential diagnosis.

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).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).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).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.II.

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.We sought to determine the effects of MET on serum hepatic parameters in PCOS patients.This was a secondary analysis of a randomized, doubled-blind trial from 2002-2004.This multi-center clinical trial was conducted in academic centers.Six hundred twenty-six infertile women with PCOS with serum liver function parameters less than twice the upper limit of normal were included.Clomiphene citrate (n = 209), MET (n = 208), or combined (n = 209) were given for up to 6 months.The percent change from baseline in renal and liver function between- and within-treatment arms was assessed.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.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.

Background: A numerical model with two pharmacokinetic parameters (the rate of diffusion into the blood (τin) and the rate of disappearance from the blood (τout)) mimicks the slow changes of follicle stimulating hormone (FSH) seen in serum. It is often desired to change serum FSH levels more rapidly. Since the pharmacokinetic parameters cannot be changed in patients, we used the model to investigate changing the amount and timing of gonadotropin administration to change FSH levels in serum more rapidly. Methods: Parameters defining the model were obtained as described previously [1]. The doses administered, and the timing of administration were individually specified. Results: The rise of serum FSH was made more rapid by administering an initial injection larger than the subsequent injections. When a rapid decrease of serum FSH was desired, administration of the new, lower dose was delayed. Conclusion: Use of a model that simulates the serum levels of FSH during gonadotropin administration provided a framework for learning how to achieve the desired serum FSH levels more rapidly in patients. With knowledge of a particular patients τin and τout, optimal FSH administration for that patient can be determined through modeling.

Background: Despite the dangers of gonadotropin administration, our understanding of serum levels of gonadotropins in our patients is poor. We created a mathematical model of gonadotropin administration in order to learn about the temporal profiles of Follicle Stimulating Hormone (FSH) levels in patients related to the doses of different gonadotropin products administered. Methods: Model parameters for each product were determined from published pharmacokinetic information available from the manufacturers. Results: For each product, serum levels of FSH rose then fell following a single injection of FSH. When a gonadotropin dose was injected repeatedly (daily), each injection resulted in a peak level of FSH that was higher than the level attained from the previous injection. Daily FSH peaks rose asymptotically, requiring 3-10 days to approach the maximum. The maximum averaged 3.5 times the peak of the first injection. Decline of FSH following the final injection required 3-10 days to approach the baseline. Time courses and peak values of FSH using different gonadotropin preparations varied widely. Conclusion: Knowledge of the slow changes of FSH that occur during modeled FSH administration will provide a framework for understanding the gonadotropin profiles that occur in patients during controlled ovarian hyperstimulation.

Background: Serum levels of follicle stimulating hormone (FSH) in patients change slowly during repeated daily injections of gonadotropin, requiring several days to achieve stable values. Using a numerical (computer) model we mimicked the serum levels of FSH using two kinetic constants that describe biological phenomena: diffusion of FSH from the injection site into the blood (τin) and disappearance of FSH from the blood by excretion/degradation (τout). We investigated the effects of these two parameters on the FSH profiles seen in the model. Methods: The parameters, τin and τout, were systematically changed to determine their effects on the delay from injection to the peak following a single injection (Tmax). Other values were investigated systematically during repeated daily injections. Results: The models parameters τin and tout affected Tmax and several features of FSH level during daily injections of gonadotropin. These included the maximum level of FSH in the serum (relative to the level attained following the first injection), the rate of rise of peaks following injections after the first, and the shortening of the delay from injection to peak. Conclusion: Knowledge of τin and τout permits us to predict serum FSH levels and time course during daily injections of gonadotropin.

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/m 2 . 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 ≥35 were less likely to ovulate than patients with BMI 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.

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. The probability of a live birth after ovulation induction in PCOS women can be estimated based on their age, body mass index, hirsutism, and duration of attempted conception.

In this prospective, randomized clinical trial, we tested the hypothesis that a needle-free CO 2 injection system (Biojector 2000) would be better tolerated by patients when compared with traditional sharp needles used for gonadotropin injections during stimulation for IVF. As measured by our questionnaire, the needle-free CO 2 injection system was not better tolerated by patients, even though it was equally effective clinically.

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/m 2 . 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.

Objective To determine the predictive value of fetal cardiac activity (FCA), measured at 6 weeks' gestation, on first-trimester pregnancy success after IVF. Design Retrospective cohort study. Setting University-based reproductive endocrinology and infertility practice. Patient(s) One hundred thirty-nine women, without a history of recurrent miscarriage, who were undergoing fresh IVF cycles from August 1, 2004 to February 28, 2005. Intervention(s) Transvaginal ultrasound. Main Outcome Measure(s) First-trimester pregnancy success. Result(s) Ninety-three percent (51/53) of gestational sacs with FCA completed the first trimester (positive predictive value of 93%). Eighty-seven percent (13/15) of sacs without FCA failed in the first trimester (negative predictive value of 87%). In singletons, the positive and negative predictive value of FCA on first-trimester success was 100%. All twin pregnancies (n = 11) successfully completed the first trimester. Conclusion(s) This analysis, which was performed strictly in an IVF population with no history of recurrent pregnancy loss, demonstrates that positive FCA at 6 weeks' gestation is an excellent predictor of first-trimester pregnancy outcome.

Objective To test the hypothesis that anovulatory women would have good pregnancy rates (PRs), regardless of single or multiple follicular development, in response to clomiphene citrate (CC), whereas ovulatory women would have good PRs only when achieving multifollicular responses to CC. Design Retrospective chart review. Setting University-based infertility center. Patient(s) Two hundred and fifty-four women underwent 585 CC-IUI treatment cycles over a 3-year period. Intervention Treatment with CC-IUI. Main Outcome Measure(s) Various factors were examined as predictors of clinical pregnancy rate (CPR) and live-birth rate (LBR) per cycle with the use of logistic regression. Result(s) Overall, the CPR was 11.1%, and the LBR was 8.7%. Of 65 clinical pregnancies, 81.5% resulted in live births (singletons, 67.7%; twins, 13.8%). There were no higher-order deliveries. In anovulatory women, the CPR and LBR were 15.7% and 13.6%, respectively. In ovulatory women, the CPR and LBR were 8.8% and 6.3%, respectively. As the number of large follicles increased from one to two, the LBR increased from 6.8% to 10.5%. Regarding the interaction of follicles with ovulatory status, anovulatory women had nearly double the CPR and LBR compared to those in ovulatory women, irrespective of the number of large follicles. Conclusion(s) Treatment with CC-IUI is more successful in anovulatory women than in ovulatory women. The multiple follicular response in both ovulatory and anovulatory women increases PRs.

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 ≥1 patent fallopian tube, normal uterine cavity, and a partner with sperm concentration ≥20 × 10 6 /mL in ≥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/m 2 (±8.7). Polycystic ovaries (PCOs) were present in 90.3% of the subjects, and the mean volume of each ovary was 10 cm 3 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 perform a systematic review of the literature to determine whether singleton pregnancies resulting from IVF-ET/GIFT are at higher risk for preterm birth ( Design Literature search and systematic review. Setting Medical school. Intervention(s) A MEDLINE search (1965–2000) was performed using the terms "premature labor," "infertility," "pregnancy complications," "gonadotropins," "pregnancy outcome," "preterm delivery," and "in vitro fertilization." Criteria for inclusion were English language, original research article, study patients conceived using IVF-ET (with or without intracytoplasmic sperm injection) or GIFT, pregnancy outcome reported compared with a control group (e.g., naturally conceived singletons at their hospital or a national reference), and prematurity clearly defined. Incomplete articles (e.g., abstracts), reports of other studies, and studies that failed to separate multiple from singleton gestations were excluded. Main outcome measure(s) Summary of relative risks of preterm birth. Result(s) Twenty-seven articles met all inclusion/exclusion criteria and were analyzed by meta-analysis. The random-effects summary relative risk of preterm birth in singleton pregnancies resulting from IVF-ET/GIFT was 1.98 (95% confidence interval, 1.77–2.22). Conclusion(s) The risk of preterm birth in singleton pregnancies resulting from IVF-ET/GIFT is twice that of natural conceived pregnancies.

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 a case of vaginal perforation during transvaginal ultrasound-guided follicle aspiration. Design Case report. Setting A university hospital. Patient(s) A 41-year-old woman who had undergone transvaginal ultrasound-guided follicle aspiration five times previously for IVF–embryo transfer. Intervention(s) Retrospective evaluation of past medical history and surgical treatment. Main outcome measure(s) Medical follow-up after surgical repair of the perforation. Result(s) Simple vaginal perforation with no damage to the gastrointestinal or genitourinary systems can be repaired at the time of perforation through the vagina. Conclusion(s) Perforation of the vagina is a possible complication of transvaginal ultrasound-guided follicle aspiration in older patients with a history of repeated transvaginal aspiration of follicles, particularly when the ovaries are difficult to visualize.

To examine the relationship between endometrial histological maturation and reproductive hormones, we studied 11 fertile women, aged 18-37 yr. All participants had had at least 1 previous pregnancy and cycled regularly, every 25-35 days. Women collected daily, first morning voided urine for measurement of estradiol and progesterone metabolite excretion, estrone conjugates (E1c), and pregnanediol glucuronide (Pdg), respectively, throughout the cycle of study. Hormones were normalized for creatinine. Between 7-9 days after home detection of a LH surge (Sure Step), participants underwent an endometrial biopsy using a small bore (Pipelle) catheter. Tissue was prepared for histological and biochemical analyses. The histological analysis is reported herein. Endometrium was dated by 3 authors (N.S., D.H., and S.P.), all of whom were blinded to the participant's identity or timing of biopsy within her cycle. Final dating was agreed upon based upon the method of Noyes et al. E1c and Pdg were integrated throughout the cycle using the trapezoidal rule, and correlations were sought between deviation from expected histology (based upon urinary hormones and LH surge) and integrated hormone values. E1c varied over a 2-fold range in these normal women, from 1196-2040 ng/cycle. Pdg excretion was much more variable, ranging from 22-119 microg/cycle. No relationship could be found between histological lagging of endometrial maturation and lower excretion of E1c. A moderate correlation was observed (Spearman's r = 0.6; P0.05) between degree of histological maturation and integrated Pdg. Of two women with evidence of a disparity between gland and stromal development (glands lagging behind stroma by2 days), one excreted 24 microg Pdg/cycle, the next to lowest value. We conclude that normal fertile women experience a wide range of hormone concentrations in the face of normal endometrial maturation. Progesterone appears to exert a dose-related effect on endometrial maturation, and the techniques we used, although relatively crude clinical measures, appeared to be sufficient to detect this relationship.

There are conflicting reports of an association of ovarian antibodies, detected by immunofluorescence, with polycystic ovary syndrome (PCOS). The objective of this study was to evaluate the association of ovarian autoimmunity with PCOS. A validated immunoassay for ovarian antibodies was used to assess serum from women with PCOS and with menopause and normal cycling women as controls. The frequency of ovarian antibodies was similar (25%) among the controls and PCOS. Thus, unlike the association of ovarian antibodies detected with this test in patients with unexplained infertility and premature menopause, the prevalence of ovarian antibody in patients with PCOS is not significantly different to controls.

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.

Objective: To study the effect of postponing hCG administration while continuing daily GnRH agonist therapy (“coasting”) on highly responsive patients undergoing IVF-ET. Design: Retrospective analysis. Setting: University-affiliated Center for Fertility and Reproductive Medicine. Patient(s): Patients undergoing IVF-ET from March 1995 to March 1997. Intervention(s): Three groups of IVF-ET patients were compared to explore the effect of coasting on cycle outcome: a group of highly responsive coasted patients, a group of equally responsive noncoasted patients, and an age-matched normally responsive control group. Two groups of coasted patients were also compared to assess the effect of E2 levels at the time that they met the follicular criteria for hCG administration. Last, the effect of varying coast duration was examined by regression analysis. Main Outcome Measure(s): Patient characteristics, outcome parameters, and incidence of ovarian hyperstimulation syndrome (OHSS). Result(s): Coasting had no detrimental effect on cycle outcome in the subset studied. Regression analysis, however, suggests an inverse relationship between coast duration and the number of mature oocytes retrieved as well as the clinical pregnancy rate. Conclusion(s): Coasting in the studied subset of IVF patients did not adversely affect cycle outcome parameters or the incidence of OHSS, but prolonged coasting intervals may impair IVF cycle outcome.

Objective To report the use of serum FSH levels during gonadotropin therapy for IVF to ensure medication compliance. Design Case report. Setting University-based reproductive endocrinology clinic. Patient(s) Two women with normal ovarian reserve undergoing IVF cycles with unexpected clinical responses. Intervention(s) FSH laboratory values. Main Outcome Measure(s) Ovarian follicular development. Result(s) Adequate follicular response leading to oocyte retrieval. Conclusion(s) Determination of serum FSH levels may help detect noncompliance with recommended gonadotropin regimens during IVF.

Objective To present a case of a patient with a duplicated left ureter presenting preoperatively as unilateral hydrosalpinx, chronic pelvic pain, and recurrent urinary tract infections (UTIs). Design Case report. Setting A large university-affiliated infertility center. Patient(s) A 37-year-old woman, para 1, with an 18-year history of recurrent UTIs associated with coitus, and chronic pelvic pain with a unilateral hydrosalpinx. Main Outcome Measure(s) Resolution of recurrent UTIs and left flank pain. Result(s) The patient has remained symptom free after laparoscopic resection of the duplicated ureter and portion of the bladder at its point of insertion. Conclusion(s) We show a rare case of a duplicated left ureter presenting as chronic pelvic pain and recurrent UTIs, demonstrating the importance of a thorough chronic pelvic pain workup.