Neurotrophins (BDNF and NGF) in follicular fluid of women with different infertility diagnoses.

Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are intra-ovarian signalling peptides that are important in follicle development and oocyte maturation. In the ovary, neurotrophin expression is regulated by gonadotrophins. Therefore, this study postulates that aetiology of infertility will affect follicular-fluid BDNF and NGF concentrations. Follicular fluid from the first follicle aspirated from 190 infertile women attending a university-affiliated fertility programme (McMaster University and ONE Fertility, Burlington, Ontario) was collected between February 2004 and November 2010. The relationship between follicular-fluid BDNF and NGF concentration and age, day-3 FSH and peak serum oestradiol concentrations and antral follicle count was determined. Participants were aged between 24 and 44 years (mean±SEM, 35.2±0.3years) of age. The median concentrations of BDNF and NGF in the follicular fluid was 19.4pg/ml and 344.6ng/ml, respectively. The concentrations of BDNF and NGF were significantly related (P=0.028) but only the BDNF concentration was significantly higher (P<0.05) in women with unexplained infertility compared with other causes of infertility. It is concluded that, apart from unexplained infertility, the underlying cause of infertility did not affect ovarian output of BDNF and NGF in response to ovulation induction.

Occult ovarian failure: a syndrome of infertility, regular menses, and elevated follicle-stimulating hormone concentrations.

Ten women with infertility, regular menses, and elevated plasma FSH concentrations after a failed in vitro fertilization attempt were studied throughout a spontaneous menstrual cycle. Plasma estradiol, progesterone, inhibin, LH, and FSH concentrations were measured by RIA on days 1, 8, 15, and 22 and compared with the ovarian steroid and gonadotropin profiles obtained from seven endocrine-normal women. The elevated FSH concentrations in the hypergonadotropic group were not associated with significant changes in E2 and P4, but an increase in LH concentrations was found on days 1, 8, and 22 (medians of 18 and 4, 17 and 6, and 7 and less than 3 U/L for the hypergonadotropic and normal groups, respectively; P less than 0.01). Their plasma inhibin concentrations [213, 242, 747, and 561 U/L (median values on days 1-7, 8-14, 15-21, and 22-28)] were normal. Autoantibodies to adrenal, thyroid, or ovary were present in five (50%) women, and antiovarian antibodies were present in 4. Two women gave a family history of thyroid disease, and one woman was hypothyroid. Repeat assessment 3-6 months revealed persistently elevated FSH concentrations in five (63%) of eight women; the other three had normal ovarian steroid and gonadotropin concentrations. The triad of infertility, regular menses, and elevated plasma FSH concentrations describes a group of women with occult ovarian failure, a condition of compensated granulosa cell function, which may be an early stage of premature ovarian failure. These women with occult ovarian failure had an impaired response to ovarian hyperstimulation and may be at increased risk of developing polyglandular autoimmunity.

Inhibin and estradiol responses to ovarian hyperstimulation: effects of age and predictive value for in vitro fertilization outcome.

We have compared the time courses of serum inhibin and estradiol responses to ovarian hyperstimulation in patients undergoing in vitro fertilization and embryo transfer as well as their predictive value for outcome of intermediate variables and pregnancy in in vitro fertilization and embryo transfer. Blood samples (n = 749) were collected for up to 6 days before hCG administration in 100 consecutive treatment cycles, of which 44 resulted in pregnancy, as defined by elevated luteal phase serum hCG beta levels. Inhibin and estradiol levels increased markedly in parallel during hyperstimulation and were highly correlated (r = 0.89; P less than 0.001). Inhibin responses were significantly lower in women 35 yr of age or older (P less than 0.001), although estradiol responses were not influenced by age. Gravidity and tubal disease also had marginal effects on the time course of inhibin responses, but not on overall mean inhibin levels or estradiol responses. The time course of hormonal responses to hyperstimulation was not influenced by any other demographic or etiological factors. Peak values of both hormones correlated with the total number of follicles (inhibin, r = 0.70; estradiol, r = 0.65; P less than 0.001) and oocytes retrieved per cycle (inhibin, r = 0.49; estradiol, r = 0.39; P less than 0.001). The time course and peak values of inhibin and estradiol responses to hyperstimulation did not differ significantly between conception or nonconception cycles whether judged by biochemical (luteal hCG beta) or clinical (viable ongoing pregnancy) criteria. Luteal phase serum inhibin, estradiol, progesterone, and hCG levels were significantly higher in conception than in nonconception cycles (P less than 0.001). These data suggest that the rises in serum inhibin and estradiol levels during hyperstimulation have similar predictive properties for IVF-ET outcomes and could, therefore, be used interchangeably to monitor hyperstimulation regimens. The age-related reduction in inhibin, but not estradiol, responses suggests that these two hormones reflect different granulosa cell functions and that serum inhibin responses to maximal ovarian stimulation may be a sensitive and early index of declining ovarian function with advancing age.

Pharmacological interventions for the induction of ovulation.

Ovulation induction is the most common medical intervention for the treatment of infertility. Clomifene is generally the first treatment choice for patients with amenorrhoea, unless there is profound hypothalamic deficiency. When clomifene fails to induce ovulation, menotropins (human menopausal gonadotrophin) or gonadotrophin-releasing hormone (GnRH) are effective, most notably in WHO group 1. In this condition associated with low estrogen and gonadotrophin levels, the aggregate of reported pregnancy rates is 25% per cycle. In hyperprolactinaemic anovulation bromocriptine reduces prolactin levels and thereby restores normal cyclicity. In all of the above conditions, the pharmacological agent addresses a specific defect in an explicit manner. WHO group 2 ovulatory disorders arise from hyperandrogenicity and other conditions that respond less predictably to gonadotrophin therapy. In women with WHO group 2 disorders, the aggregate of reported pregnancy rates is 8%. Ovulation induction is also used in ovulatory infertile women to generate multiple follicles and increase the likelihood of fertilisation. The aggregate of pregnancy rates in clomifene trials was 7% per cycle, and 6% in gonadotrophin trials. Gonadotrophin therapy is more effective, however, in association with assisted reproduction techniques. The contrasting treatment success in discrete disorders (25% per cycle) and heterogeneous disorders such as WHO group 2 and persistent infertility (6 to 8% per cycle) underlines the need for research to discover specific causal mechanisms and identify explicit new pharmacological interventions.

The measurement of surface area of endometriotic implants by morphometric analysis.

There are numerous staging methods for the assessment and evaluation of endometriosis both before and after treatment. Present systems rely on subjective criteria that are prone to bias and error. This report describes an objective technique for the measurement of surface area of pelvic endometriotic implants that is both accurate and reproducible. Six patients with endometriosis underwent laparoscopy and were staged using the Revised American Fertility Society criteria; the lesions were photographed simultaneously. These patients were then treated with either danazol or Nafarelin acetate for 6 months before a second-look laparoscopy. Using coded photographic slides, implants were measured using computerized morphometric analysis. An accurate record of the number and surface area of the lesions was obtained before and after treatment. The mean surface area of individual lesions and the total visible disease per patient fell by 89 and 82%, respectively. The mean number of lesions per patient actually rose by 30% as a result of fragmentation into smaller plaques. These data suggest that morphometry may be more valuable in the assessment of endometriotic implants than are all previously described staging systems.

Dinoprostone vaginal insert for cervical ripening and labor induction: a meta-analysis.

OBJECTIVE: To compare dinoprostone 10 mg controlled-release vaginal insert with other forms of vaginal or cervical prostaglandin for cervical ripening. DATA SOURCES: Literature search strategy included review of the Cochrane database of randomized trials, on-line searching of MEDLINE, hand searching of bibliographies, and contact with authors of relevant reports. METHODS OF STUDY SELECTION: Randomized trials were included if they compared a dinoprostone slow-release vaginal insert with an alternative vaginal or cervical prostaglandin for cervical ripening and labor induction in women at term with singleton gestations. Primary end points were delivery by 24 hours postinsertion, uterine hypertonus with fetal heart change, and cesarean delivery rate. Study inclusion, validity assessment, and data extraction were carried out independently by two reviewers, and cross-checked for consistency. Data were combined when appropriate, using the Mantel-Haenszel fixed-effects method. Statistical heterogeneity was assessed using chi-square statistics. TABULATION, INTEGRATION, AND RESULTS: Nine relevant trials were identified, seven comparing the dinoprostone 10 mg vaginal insert with dinoprostone gel and two with misoprostol. Five trials reported adequate methods for randomization concealment. None were double blind. The likelihood of delivery by 24 hours was similar with the vaginal insert and alternatives: common odds ratio (OR) 0.80 (95% confidence interval [CI] 0.56, 1.15). Uterine hypertonus with change in fetal heart and cesarean delivery rate were also similar: common OR 1.19 (95% CI 0.56, 2.54) and 0.78 (95% CI 0.56, 1.08), respectively. The secondary end points of mean time to delivery and delivery by 12 hours appeared to favor misoprostol-dinoprostone gel. However, data for these end points were heterogeneous and their combination is therefore of limited value and potentially misleading. CONCLUSION: No clinically significant differences were identified between the vaginal insert and alternatives used for cervical ripening at term.

Primary amenorrhea associated with hyperprolactinemia: four cases with normal sellar architecture and absence of galactorrhea.

Hyperprolactinemia is an uncommon cause of primary amenorrhea. The diagnosis should be sought even in the absence of galactorrhea and sellar abnormality, particularly when thelarche and pubarche have occurred. Reduction of serum PRL levels followed by menarche can be anticipated within a few months of starting bromocriptine therapy in the majority of cases.

Does cigarette smoking impair natural or assisted fecundity?

OBJECTIVES: To assess the effects of female and male smoking on natural and assisted fecundity. DESIGN: A systematic review of published studies was conducted, identifying reports using on-line and hand search techniques. INCLUDED STUDIES: Potentially relevant articles were screened for inclusion based on the following criteria: comparative study (cohort or case control) with clinical pregnancy or live birth reported among smokers and nonsmokers. EXPOSURE: Cigarette smoking. MAIN OUTCOME MEASURES: Time to conceive; conceptions per subject or per cycle; spontaneous abortion rate. RESULTS: Thirteen relevant studies of natural conception were identified. All but one demonstrated a negative association between smoking and fecundity (odds ratio [OR] for conception or live birth 0.33 to 1.0). Seven studies of IVF-GIFT yielded a common odds ratio for conception of 0.57 (95% confidence interval 0.42 to 0.78). Seven studies evaluating spontaneous abortion suggested a small increased risk among female smokers (OR 0.83 to 1.8). Twenty-one studies assessing smoking in men demonstrated no consistent effect on sperm quality. None of the four studies evaluating fertility in male smokers demonstrated significant impairment. CONCLUSION: This body of literature suggests a small but clinically significant detrimental effect of female smoking on both time to conception and spontaneous abortion risk. Variability between studies, particularly in terms of adjustment for confounding factors, undermines the strength of these conclusions. However, the consistent dose-response effect in both the spontaneous conception and abortion literature and a return to normal fecundity among exsmokers suggest a causal association. The effect of male smoking on fecundity is probably far less significant.

Funding in vitro fertilization treatment for persistent subfertility: the pain and the politics.

OBJECTIVE: To consider the arguments for and against funding for in vitro fertilization (IVF) and to explore potential avenues for policy change. DESIGN: Narrative literature review, policy analysis. SETTING: University Department of Obstetrics and Gynecology. PATIENT(S): Sub-fertile women and men. INTERVENTION(S): Fertility treatments, in particular IVF. RESULT(S): The two main arguments used against funding for IVF are that [1] subfertility is a social, not a medical problem, and therefore its treatment is not medically indicated or necessary, and [2] the clinical effectiveness of IVF is unproven. These and other major arguments are critiqued. CONCLUSION(S): Dismissing IVF as medically unnecessary seems premature because medical necessity has not been operationally defined. Demonstrating IVF effectiveness through a randomized trial has not been done but is feasible: a multicenter trial is currently underway in Canada. Dealing with the concern that subfertility treatment challenges the role of women in society, as well as with questions of cost-effectiveness, are more difficult challenges that deserve further debate. The potential for unethical uses and broader social implications of IVF add to its dubious status and provide a convenient rationale for refusing to pay. However, none of these concerns is unique to IVF: many currently covered health services are susceptible to the same criticisms. For all services, judgments of eligibility for coverage should be consistent and transparent and should explicitly separate the issues of cost from other factors.

A prospective study of prognostic factors in in vitro fertilization and embryo transfer.

Multiple factors influence the outcome of in vitro fertilization and embryo transfer (IVF-ET). This prospective study was designed to assess their relative importance, in order to improve prognostic ability and treatment success. Prior to IVF-ET, couples were divided into "good" (GP) and "poor" (PP) prognosis groups according to female age, semen quality, previous response to stimulation, and embryo quality. The data obtained from 716 consecutive treatment cycles then were evaluated using univariate statistics and logistic regression, a technique designed to assess the relative contribution of significant factors. The pregnancy rate per GP cycle was 14.7%, compared with 5.4% per PP cycle (chi 1(2) = 12.7, P less than 0.001). The most important prognostic factors were female age, the pregnancy rate showing a linear decline after the age of 25, and previous failed fertilization due to abnormal sperm. The rate of pregnancy also declined after 14 or more follicles were aspirated and/or nine oocytes were retrieved. A formula for the probability of pregnancy, derived from the logistic regression, provides patients with a more accurate prognosis before treatment.

A quantitative overview of controlled trials in endometriosis-associated infertility.

OBJECTIVE: To undertake quantitative overviews of the following commonly used treatments for endometriosis-associated infertility: ovulation suppression, laparoscopic ablation, and conservative laparotomy. DESIGN: A protocol was prospectively defined detailing the research question, mode of study identification, inclusion and exclusion, data extraction, and pooling methods. Studies were assessed for relevance and validity by independent reviewers and their findings compared. Data were extracted in a similar fashion. PATIENTS: Women with visually diagnosed endometriosis, complaining of infertility. MAIN OUTCOME MEASURE: Pregnancy as defined by positive pregnancy test. RESULTS: Twenty-five relevant randomized controlled trials and cohort studies were identified with a total of 37 treatment comparisons. The common odds ratio (OR) from seven studies comparing ovulation suppression (danazol, medroxyprogesterone acetate [MPA], or gestrinone) versus placebo or no treatment was 0.85, suggesting no treatment benefit. The common OR for pregnancy after ovulation suppression (MPA, gestrinone, or GnRH agonist) versus danazol was also nonsignificant: 1.07. Although pooled data from trials of laparoscopic surgery suggested a treatment benefit, significant heterogeneity between studies undermines this conclusion. Laparoscopic data were similar to those from conservative laparotomy studies. Studies assessing conservative surgery plus danazol versus danazol alone showed no significant benefit from this adjunct. CONCLUSION: Ovulation suppression is an ineffective treatment for endometriosis-associated infertility. Well-designed trials of laparoscopic ablation deserve a high priority.

Delayed-type hypersensitivity to human gonadotropin: case report.

OBJECTIVE: To investigate adverse reactions to hMG preparations in two women in IVF programs. DESIGN: Two case reports with skin tests for delayed hypersensitivity (DH) to hMG and a biopsy of one delayed reaction. SETTING: Allergy and infertility clinics in university medical center. PATIENTS: Two affected patents with a history of local reactions to the injected hMG, one of whom also had fever, and nine control subjects. INTERVENTIONS: Skin tests and biopsy. MAIN OUTCOME MEASURES: Delayed hypersensitivity skin response to hMG in affected patients indicated by timing and biopsy results. Negative skin test with the purified hFSH, which was also used in treatment with no adverse effects. CONCLUSION: Use of the purified preparation avoids DH reaction.

Ultrasound-guided fallopian tube catheterization per vaginum: a feasibility study with the use of laparoscopic control.

The fallopian tube can be cannulated per vaginum under ultrasound control. The sensation and ultrasound appearance of smooth passage without visible kinking are accurate predictors of success. The average time taken for each cannulation was 7.2 minutes. Adequate practice in non treatment cycles is essential before proceeding to cell transfer, while further modification of the catheters used may improve overall success.

Homologous artificial insemination for oligoasthenospermia: a randomized controlled study comparing intracervical and intrauterine techniques.

Homologous artificial insemination (AIH) is used to treat infertility caused by oligoasthenospermia, despite the lack of controlled studies confirming its benefit. This prospective randomized controlled trial was undertaken to determine whether intracervical (IC-AIH) or intrauterine (IU-AIH) homologous artificial insemination improves pregnancy rates in couples with infertility attributable to oligoasthenospermia alone. Twenty couples were randomized to receive IC-AIH or IU-AIH. Sixty-three insemination cycles were completed. During the same study period, 35 cycles with timed vaginal intercourse alone were assessed. Four pregnancies occurred, all following timed vaginal intercourse. No pregnancies resulted from IC-AIH or IU-AIH. This suggests that neither IC-AIH nor IU-AIH is of benefit when oligoasthenospermia is the cause of infertility. Pregnancies previously attributed to AIH may also have been conceived as a result of vaginal intercourse. This confounding effect on the results of AIH should always be considered.

The role of luteal phase support in infertility treatment: a meta-analysis of randomized trials.

OBJECTIVE: To determine whether the use of luteal phase support improves pregnancy rate (PR) in infertility. DESIGN: A meta-analysis of randomized trials of luteal phase support. Search of the National Library of Medicine MEDLINE data base from 1971 using the words luteal, pregnancy, human, and comparative. Bibliography of relevant articles, reviews, and abstracts of scientific meetings were hand searched. All randomized controlled trials of luteal phase support in infertility were included. Luteal phase support for recurrent abortion and nonrandomized trials were excluded. The common odds ratio was calculated for each intervention using the Mantel-Haentzel test. Homogeneity of treatment effect was evaluated using the Breslow-Day test. MAIN OUTCOME MEASURES: Pregnancy per cycle, rate of spontaneous abortion, and ovarian hyperstimulation syndrome rate. RESULTS: Eighteen trials met the above criteria. Human chorionic gonadotropin improved PRs in IVF when GnRH agonist (GnRH-a) was used (n = 151) and was superior to P (n = 352). Its benefit in all IVF cycles, however, was not established because of significant heterogeneity of treatment effect. Progesterone improved the PR in all IVF cycles (n = 457). No significant reduction in spontaneous abortion was noted with luteal support (n = 200). Ovarian hyperstimulation syndrome occurred in 5% of patients with hCG. Combination of data from trials of luteal support with other infertility therapies was not possible because of the differences in patient populations. CONCLUSIONS: The meta-analysis supports the routine use of hCG in IVF cycles using a GnRH-a. Progesterone was also beneficial for luteal phase support in IVF. For other infertility therapy, however, further research is needed to evaluate the role of luteal phase support.

Follicle-stimulating hormone versus human menopausal gonadotropin for in vitro fertilization cycles: a meta-analysis.

OBJECTIVE: To conduct a systematic overview of available data comparing FSH with hMG in IVF treatment cycles. DESIGN: A meta-analysis of randomized trials of FSH versus hMG use in ovarian stimulation protocols, with or without GnRH agonists, in IVF treatment cycles. Search strategies included on-line searching of the National Library of Medicine MEDLINE data base from 1975 to 1993 and hand searching of bibliographies of relevant publications and reviews and abstracts of scientific meetings. Common odds ratio (OR) and overall absolute treatment effect were calculated after demonstrating homogeneity of treatment effect across all trials. MAIN OUTCOME MEASURES: Clinical pregnancy rates per cycle start, per cycle reaching oocyte retrieval, and per cycle reaching ET. RESULTS: Eight trials met the inclusion criteria. The overall OR in favor of FSH for cycle start, oocyte retrieval, and ET were 1.71, 1.69 and 1.70, respectively, and represented an overall absolute treatment effect of 8.5%, 8.0% and 8.3%, respectively. CONCLUSIONS: This meta-analysis demonstrates that in IVF cycles the use of FSH is associated with a significantly higher clinical pregnancy rate than hMG.

Randomized trial of a "stage-of-change" oriented smoking cessation intervention in infertile and pregnant women.

OBJECTIVE: To assess a "stage-of-change" oriented smoking cessation intervention for infertile and pregnant women, compared with standard of care. DESIGN: Randomized controlled trial. SETTING: Three university teaching hospitals in Hamilton, Ontario, Canada. PATIENT(S): Infertile women at their first visit to a tertiary referral infertility clinic (n = 94) and new patients seeking pre-natal care (n = 110) who had smoked >/= 3 cigarettes in the past six months. INTERVENTION(S): A three to five minute scripted intervention and booklet specific to the woman's "stage-of-change" in the smoking continuum, versus standard of care. Exhaled carbon-monoxide (CO) monitoring was used to validate exposure in both groups. MAIN OUTCOME MEASURE(S): Delta "stage-of-change" and rate of maintained cessation at 12 months post follow-up. RESULT(S): Intervention and control were similarly effective for infertile women: the rate of maintained cessation rose significantly from 4% to 24% over twelve months, with a mean delta "stage-of-change" 0.28. In prenatal women, neither approach was effective. Maintained cessation did not significantly change from 0 to 12 months (19% to 18%). Mean delta "stage-of-change" declined by -0.62. CONCLUSION(S): For infertile women, basic information describing the impact of smoking on fertility, along with exhaled CO monitoring and a more intensive intervention were both highly effective. In pregnant women neither approach was beneficial, with some evidence of post-partum relapse.

Cigarette smoking and the outcomes of in vitro fertilization: measurement of effect size and levels of action.

OBJECTIVE: To assess whether cigarette smoking in women or men affects the outcomes of IVF-ET and at what functional levels smoking is active. INTERVENTIONS: Demographic and smoking data were collected by questionnaire at the onset of consecutive treatment cycles (n = 462) and at the time of ET. In addition to routine endocrine and clinical data, circulating immunoreactive inhibin, follicular fluid E2 endometrial thickness, and morphology were assessed. Reported exposure to cigarettes was validated using a serum cotinine assay. RESULTS: Serum cotinine level at the onset of treatment correlated strongly with the number of cigarettes reported (r = 0.68). The duration and dose of gonadotropin treatment was greater among active smokers than never smokers: 10.2 versus 9.2 days and 24.7 versus 19.8 ampules, respectively. Fertilization, pregnancy, and abortion rates were similar between groups. Multivariate analyses demonstrated negative correlation between female age, but no such effect was seen with female or male smoking. Sperm concentration was significantly reduced in male smokers (prewash: 108 versus 130 x 10(6); postwash: 17.1 versus 21.6 x 10(6)), although fertilization rate was unaffected (66% versus 62%). Follicular function, assessed using serum inhibin and E2, as well as follicular fluid E2 levels showed no significant difference between active smokers and never smokers. Endometrial thickness and morphology also were similar between groups. CONCLUSIONS: These data suggest that among couples undergoing IVF neither female nor male smoking has a measurable deleterious effect on conception rate. Female age remains a far more potent prognostic factor in the current study. However, when all the published data are combined, a significant deleterious effect of smoking on conception is suggested, with a common odds ratio of 0.540 (95% confidence interval 0.385 to 0.757).

Serum immunoactive inhibin levels in early pregnancy after in vitro fertilization and embryo transfer.

OBJECTIVE: To determine the maternal serum concentrations of inhibin, E2, P, and hCG in early pregnancies arising from IVF and ET or GIFT and to assess the value of these hormone measurements in determining outcome of pregnancy. DESIGN: Serum immunoactive inhibin, E2, P, and hCG levels were measured in the first trimester of pregnancies after IVF-ET and GIFT procedures. SETTING: In vitro fertilization and ET or GIFT was undertaken at Monash IVF, Melbourne, Victoria, Australia. PATIENTS: At least two blood samples were collected from 117 women between 4 and 11 weeks of gestation. MAIN OUTCOME MEASURES: The hormone concentrations in the IVF-ET and GIFT pregnancies were compared with those in pregnancies and related to outcome of pregnancy. RESULTS: Serum inhibin levels in singleton pregnancies were significantly higher than in comparable normal pregnancies. In contrast to normal conceptions in which inhibin concentrations rose to peak at 11 weeks, the levels found in IVF-ET and GIFT singleton pregnancies were high at 5 weeks' gestation and declined subsequently. In twin pregnancies, the inhibin levels were significantly greater than those in singleton pregnancies. In biochemical pregnancies diagnosed by increasing hCG concentrations in the absence of an embryonic sac, inhibin levels were significantly lower than those found in singleton pregnancy, as were E2, P, and hCG levels. In anembryonic pregnancies, diagnosed by the confirmation of an intrauterine gestation sac with no evidence of a fetal complex, inhibin concentrations were highest at week 4 and declined, being significantly lower at all stages of gestation. In ectopic pregnancy, serum inhibin levels were lower at all stages of gestation, whereas E2 concentrations were not lower until 6 weeks and P levels until week 5. Serum hCG levels were significantly lower at all stages of gestation. In women with spontaneous abortions, inhibin levels were lower than singleton pregnancies at 7 weeks. CONCLUSIONS: Serum inhibin concentrations are elevated in pregnancies arising from ovarian hyperstimulation in the first trimester when compared with those in normal pregnancy, probably as a result of the presence of multiple corpora lutea resulting from ovarian hyperstimulation. Serum inhibin, E2, P, and hCG are useful markers of abnormal pregnancy outcome.