Diagnosis of parental balanced reciprocal translocations by trophectoderm biopsy and comprehensive chromosomal screening.

PURPOSE: This study investigates a case series of eight couples who underwent trophectoderm (TE) biopsy and comprehensive chromosomal screening (CCS) for routine aneuploidy screening and were found to have CCS results concerning for previously undetected parental balanced reciprocal translocations. METHODS: In each case, controlled ovarian hyperstimulation and in vitro fertilization (IVF) yielded multiple blastocysts that each underwent CCS with high-density oligonucleotide microarray comparative genomic hybridization (aCGH). RESULTS: Parental translocations were suspected based on the finding of identical break point mutations in multiple embryos from each couple. Confirmation of these suspected translocations within blastocysts was performed with next-generation sequencing (NGS). Subsequent parental karyotypic evaluation resulted in a diagnosis of parental balanced reciprocal translocation in each case. CONCLUSIONS: We demonstrated that high-resolution aCGH and NGS on TE biopsies can accurately detect parental reciprocal translocations when previously unrecognized.

Endometriosis-associated infertility.

This review summarizes the recent literature examining the relationship between endometriosis and infertility. It is clear that the advanced stage of the disease and the mechanical disruption of the pelvic anatomy may cause infertility. The link between early stage endometriosis and infertility remains a source of controversy. Management plans must be individualized contingent upon the stage of disease, the age of the patient and the duration of infertility. The preponderance of data suggests that ablative therapy at the time of laparoscopy is as good as, or superior to expectant or medical therapy. With the exception of IVF/ET, ovarian suppression with GnRH agonists is not warranted in endometriosis-associated infertility. Controlled ovarian hyperstimulation with IUI is appropriate therapy in women with minimal-to-mild and surgically corrected endometriosis.

Sequential clomiphene citrate and human menopausal gonadotrophin with intrauterine insemination: the effect of patient age on clinical outcome.

The purpose of this investigation was to examine the influence of female and male patient age on pregnancy rates with sequential clomiphene citrate (CC) and human menopausal gonadotrophin (HMG) ovulation induction with intrauterine insemination (IUI) therapy after previous CC and IUI treatment failure. A total of 208 patients previously unable to conceive with CC/IUI therapy underwent 416 treatment cycles of sequential CC/HMG with IUI at a university fertility centre between May, 1991 and August, 1995. Clinical pregnancy rates, live birth rates, and the effect of female and male partner chronological age were retrospectively examined. Treatment with sequential CC/HMG with IUI resulted in clinical pregnancy rates ranging from 5.9 to 23.1% despite previous CC/IUI treatment failure. Clinical pregnancy rates, live birth rates, and cumulative pregnancy rates declined significantly in female patients > or = 35 years of age compared to those < 35 years of age. A statistically significant decline in clinical pregnancy rates could not be demonstrated as a function of increasing male partner age. Pregnancy rates in patients undergoing ovulation induction with sequential CC/HMG with IUI decline significantly with increasing female partner age.

Androgen response to hypothalamic-pituitary-adrenal stimulation with naloxone in women with myotonic muscular dystrophy.

Myotonic muscular dystrophy (MMD) is a disease of autosomal dominant inheritance characterized by multisystem disease, including myotonia, muscle-wasting and weakness of all muscular tissues, and endocrine abnormalities attributed to a genetic abnormality causing a defective cAMP-dependent kinase. We have previously reported that MMD patients demonstrate ACTH hypersecretion after endogenous CRH release stimulated by naloxone administration while manifesting a normal cortisol (F) response. Additionally, others have reported a reduced adrenal androgen (AA) response to exogenous ACTH administration in MMD patients. As ACTH stimulates the secretion of both AAs and F, it is possible that the discordant relationship of these hormones in MMD patients results from a defect of adrenocortical ACTH receptor function or postreceptor signaling or subsequent biochemical events. Furthermore, the molecular abnormality seen in MMD patients may suggest that the mechanism underlying the frequently observed discordances in the secretion of glucocorticoids and AAs (e.g. adrenarche, surgical trauma, severe burns, or intermittent glucocorticoid administration) are explainable solely via an alteration in the function of the ACTH receptor or postreceptor signaling. To ascertain whether the responses of F and AAs to endogenous ACTH diverged in this disorder, we prospectively studied the responses of these hormones to naloxone-stimulated CRH release in nine premenopausal women with MMD and seven healthy age and weight-matched control women. After naloxone infusion (125 micrograms/kg, i.v.), blood sampling was performed at baseline (i.e. -5 min) and at 30 and 60 min. In addition to the absolute hormone level at each time, we calculated the net increment (i.e. change) at 30 and 60 min and the area under the curve (AUC) for F, ACTH, dehydroepiandrosterone (DHA), and androstenedione (A4). Consistent with our previous study, MMD patients demonstrated higher ACTH levels at all sampling times except [minud]5 min. AUC analysis revealed the ACTHAUC values were significantly higher in MMD than in control women (457 +/- 346 vs. 157 +/- 123 pmol/min.L; P < 0.03), whereas the FAUC response did not differ between MMD and controls (13860 +/- 3473 vs. 13375 +/- 3465 nmol/min.L; P > 0.5). Despite the greater ACTH secretion, the baseline circulating dehydroepiandrosterone sulfate levels were significantly lower in MMD compared with control women (18 +/- 23 vs. 61 +/- 23 mumol/L; P < 0.002). The serum concentrations of A4 at baseline, 30 min, and 60 min and DHA levels at 30 and 60 min were also significantly lower in MMD vs. control women. Additionally, the A4AUC and DHAAUC values were significantly lower in MMD patients than in controls. Furthermore, the net response of DHA at 60 min to the endogenous ACTH increase was also reduced in MMD patients compared with that in control subjects (2.3 +/- 2.1 vs. 5.6 +/- 2.6 nmol/L; P < 0.02). In conclusion, in addition to ACTH hypersecretion to CRH-mediated stimuli, these data suggest that MMD patients have a defect in the adrenocortical response to ACTH, reflected in normal F and reduced DHA and A4 secretion. Whether this defect is inherent to the disease or simply reflects adaptive changes to chronic disease remains to be demonstrated. However, it is possible that further studies of the response of MMD patients to ACTH may reveal a mechanism that explains the frequently observed dichotomy in the secretion of glucocorticoids and AAs.

Infertile women of advanced reproductive age. Variability of day 3 FSH and E2 levels.

OBJECTIVE: To evaluate the variability of basal (day 3) levels of follicle stimulating hormone (FSH) and estradiol (E2) in infertile women of advanced reproductive age. STUDY DESIGN: Retrospective analysis of day 3 FSH and E2 concentrations measured serially in patients of advanced reproductive age at a tertiary university fertility center. RESULTS: Forty-seven infertile women > or = 38 years of age (range, 38-47) undergoing ovulation induction therapy had basal FSH and E2 levels measured on two or more cycles within a two-year periods. During the study period all live births occurred in patients with day 3 FSH values < or = 13 mIU/mL and E2 values < or = 80 pg/mL, and these values were used as normative cutoffs for favorable ovarian reserve. Eleven of 38 women (28.9%) demonstrated a shift in basal values of FSH and/or E2 from the normal to the abnormal range in a subsequent cycle. Of these 11 women, 10 (90.9%) demonstrated a shift of only one hormone (FSH, n = 6) or (E2, n = 4) from the normal to the elevated range. One of 47 women (2.1%) had a shift of both basal FSH and E2 from the normal to the elevated range in a subsequent cycle. All patients who presented with or later developed an elevated day 3 level of FSH and/or E2 had persistent elevations of one or both hormones in all subsequent measurements. CONCLUSION: Day 3 FSH and/or E2 concentrations shifted from the normal to the abnormal range in 28.9% of an infertile patient population of advanced reproductive age screened serially within a two-year period. We hypothesize that serial assessment of basal FSH in combination with E2 will improve the ability to detect diminished ovarian reserve in infertile women of advanced reproductive age.

Basal estradiol and follicle-stimulating hormone predict fecundity in women of advanced reproductive age undergoing ovulation induction therapy.

OBJECTIVE: To determine the prognostic value of single basal E2 and FSH levels as predictors of fecundity in women of advanced reproductive age who are undergoing ovulation induction with IUI therapy. DESIGN: Prospective, observational. SETTING: Fertility service of university medical center. PATIENT(S): Infertile couples in which the female partner was > or = 38 years old. INTERVENTION(S): Single assessment of basal E2 and FSH levels and ovulation induction with IUI. MAIN OUTCOME MEASURE(S): Cumulative and clinical pregnancy rates and live birth rates. RESULT(S): All live births occurred in patients with a basal E2 < or = 80 pg/mL (conversion factor to SI unit, 3.671), a basal FSH < or = 13 mIU/mL (conversion factor to SI unit, 1.00), and a chronological age < or = 42 years. In women 38 to 42 years of age, 10.3% had elevated basal E2 (> 80 pg/mL) in combination with normal basal FSH (< or = 13 mIU/mL), and no live births occurred in these couples. The cumulative live birth rate after four treatment cycles in women 38 to 42 years of age with both normal basal E2 (< or = 80 pg/mL) and FSH levels (< or = 13 mIU/mL) was 43.9%. CONCLUSION(S): Basal E2 improves the ability to predict fertility potential compared with basal FSH and chronological age alone. Basal E2, in combination with basal FSH and chronological age, has useful prognostic value in prospectively counseling patients of advanced reproductive age who are considering ovulation induction and IUI therapy.

Impact of overnight dexamethasone suppression on the adrenal androgen response to an oral glucose tolerance test in women with and without polycystic ovary syndrome.

In order to test the hypothesis that adrenocortical overactivity, possibly related to the stress of testing, may impact on the measurement of circulating androgen concentrations during glucose-induced hyperinsulinaemia, we prospectively screened 10 patients with the polycystic ovary syndrome (PCOS) and nine healthy control women with an oral glucose tolerance test (OGTT), before and after the administration of dexamethasone. Blood sampling was performed at 0, 30, 60, 90, and 120 min following the oral ingestion of 75 g of glucose, before and after the administration of 1.0 mg dexamethasone on the evening prior to testing. Total and free testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), cortisol, glucose and insulin were assessed during the 2 h OGTT. Women with PCOS had increased basal concentrations of free testosterone, total testosterone, androstenedione, and insulin compared to control women. In women with PCOS an acute decline in circulating concentrations of DHEAS occurred during the OGTT. In PCOS women there were no changes in other ovarian or adrenal androgens during OGTT before or following dexamethasone administration. In control women DHEA concentrations declined during the OGTT. Following overnight dexamethasone suppression in control women, circulating concentrations of DHEAS and testosterone also declined. It is concluded that: (i) in PCOS women only the concentration of circulating DHEAS decreased during glucose-induced hyperinsulinaemia and dexamethasone administration did not further alter androgen responses to an OGTT; (ii) it is possible that, in these hyperandrogenic patients, the insulin-related suppression of adrenocortical testosterone and DHEA is negated by their much greater ovarian secretion of these androgens; (iii) in control women DHEA concentrations acutely declined during the OGTT and the administration of dexamethasone resulted in the acute decline of DHEA, DHEAS, and testosterone; (iv) it appears that the stress related to testing impacts on the androgen response to OGTT, at least in healthy women.

Female and male partner age and menotrophin requirements influence pregnancy rates with human menopausal gonadotrophin therapy in combination with intrauterine insemination.

This study analyses the influence of female and male patient age and human menopausal gonadotrophin (HMG) requirements on clinical pregnancy rates and live birth rates with ovulation stimulation using HMG in combination with intrauterine insemination (IUI). In this study, 363 consecutive HMG/IUI treatment cycles in 184 patients carried out at a university fertility centre were analysed in a retrospective fashion. The main outcomes measured were clinical pregnancy rates and live birth rates. Increased female partner age (> or = 35) and male partner age (> or = 40) were found to negatively influence pregnancy rates with HMG/ IUI therapy. In addition, this study demonstrated a critical threshold of HMG requirements beyond which pregnancy did not occur. No pregnancies occurred in treatment cycles requiring > 25 ampoules (1875 IU) of menotrophins to achieve follicular maturity, irrespective of patient age. In conclusion, female partner age, male partner age, and HMG requirements all significantly influence pregnancy rates with HMG/IUI therapy.

Serum immunoreactive leptin concentrations in women with polycystic ovary syndrome.

Recent data in the mouse demonstrate that leptin, a protein hormone produced by fat cells, is required for fertility. In the absence of leptin the mice become obese, diabetic and infertile. Polycystic ovary syndrome (PCOS), a common cause of infertility in women, is associated with obesity and insulin resistance. Because of the increased frequency of PCOS in obese women we tested the hypothesis that alterations in serum leptin concentrations might be associated with PCOS. Immunoreactive leptin concentrations were measured in 58 women with PCOS and 70 regularly menstruating (control) women. As has previously been shown there was a positive correlation between leptin levels and body mass index (BMI). Although the leptin levels in the majority of women with PCOS fell within the control range, 29% of PCOS women had leptin levels above the 99% prediction interval for their BMI and none had low leptin levels. There were also positive correlations of leptin levels with free testosterone and insulin sensitivity in control women. In women with PCOS, 13% and 9.5% exhibited higher than expected leptin concentrations with respect to free testosterone and insulin sensitivity, respectively. Insulin resistant PCOS women had higher leptin levels than controls. The data demonstrate that a substantial proportion of women with PCOS have leptin levels that are higher than expected for their BMI, free testosterone and insulin sensitivity. These results suggest that abnormalities in leptin signaling to the reproductive system may be involved in certain cases of PCOS.

Discrimination between chronological and ovarian age in infertile women aged 35 years and older: predicting pregnancy using basal follicle stimulating hormone, age and number of ovulation induction/intra-uterine insemination cycles.

A marked decline in fertility rates has been demonstrated in women > 35 years of age. We have previously demonstrated the importance of basal follicle stimulating hormone (FSH) concentrations plus chronological age to predict pregnancies in women aged >/=40 years undergoing ovulation induction therapy. The purpose of the current study was to extend our previous study and determine the impact of age, basal FSH concentrations and ovulation induction/inter-uterine insemination (IUI) treatment cycles on pregnancy rates in infertile women age >/=35 years. This prospective observational study was performed at a tertiary university fertility centre. Assessments of basal hormonal status and ovulation induction protocols were performed. The main outcome measured was clinical pregnancies. A total of 770 treatment cycles in 179 women aged >/=35 years were analysed. The impact of basal FSH concentrations on treatment outcomes could be bifurcated into a favourable group (FSH /= mIU/ml). A multivariate logistic regression model was generated which accurately predicted pregnancies. There was a high degree of correlation between predicted pregnancies and observed pregnancies (r = 0.86). We conclude that age, number of treatment cycles and the interaction term basal FSH x age are useful and significant predictors of pregnancies in patients aged >/=35 years undergoing ovulation induction/IUI therapy.

Clomiphene citrate with intrauterine insemination: is it effective therapy in women above the age of 35 years?

OBJECTIVES: To evaluate the influence of female age on clomiphene citrate (CC) with IUI therapy and to compare the efficacy of this therapy between patients with ovulatory and anovulatory infertility. SETTING: A university fertility clinic. SUBJECTS: Six hundred sixty-four CC with IUI cycles from 290 women aged 22 to 48 years. MAIN OUTCOME MEASURES: Cumulative and clinical pregnancy rates (PRs). RESULTS: Both cumulative and clinical PRs declined substantially in women > 35 years when compared with those < or = 35 years. In addition, no difference in these parameters was noted between patients with ovulatory and anovulatory infertility diagnoses. The vast majority of pregnancies occurred within the first four treatment cycles, irrespective of age or ovulatory versus anovulatory infertility diagnoses. CONCLUSIONS: The age-related decline in clinical PR is most rapid beginning at the age of 35 years. For any given age group, CC with IUI therapy has similar cumulative and clinical PRs for both ovulatory and anovulatory infertility diagnoses. This therapy usually should not extend beyond four cycles. Couples should be counseled about the dramatic fall in PRs occurring beyond the age of 35 years.

Polycystic ovary syndrome: pathophysiology and outcome with in vitro fertilization.

OBJECTIVE: To assess the efficacy of IVP-ET in infertile women with the polycystic ovary syndrome (PCOS) and to provide a comprehensive review of contemporary therapeutic options and their complications as reflected in the current literature. DESIGN: Pertinent studies in medical literature identified through computerized bibliographic search and via manual review of relevant scientific publications. RESULTS: In vitro fertilization and ET is an effective therapy for PCOS patients who are refractory to ovulation induction in vivo or who have coexisting infertility factors. The use of GnRH agonist (GnRH-a) is associated with significant reductions in the incidence of pregnancy loss and may improve fertilization and cleavage rates. In the PCOS patient, the use of purified FSH preparations does not appear to improve pregnancy rates nor other clinical parameters when compared with hMG. Severe ovarian hyperstimulation syndrome (OHSS) is an important consideration when PCOS patients undergo superovulation protocols. Strategies for OHSS prevention include the use of intravenous albumin immediately after oocyte retrieval, triggering of ovulation with a GnRH-a, or withholding menotropin therapy for several days before hCG administration. Cryopreservation of all embryos for future transfer in an artificial cycle has also proven to be an effective alternative in PCOS patients at high risk for severe OHSS. CONCLUSIONS: Pregnancy rates for PCOS patients undergoing IVF-ET are comparable with those for women with tubal factor infertility. Therefore, IVF-ET should be offered to patients with PCOS who are refractory to conventional infertility modalities.

The profound impact of patient age on pregnancy outcome after early detection of fetal cardiac activity.

OBJECTIVE: To evaluate the influence of maternal age on pregnancy loss rates after early documentation of fetal cardiac activity by transvaginal ultrasound (US) in previously infertile women. DESIGN: Retrospective, observational study. SETTING: Tertiary fertility center. PATIENTS: One hundred eighty-six previously infertile women 20 to 43 years of age undergoing ovulation induction. MAIN OUTCOME MEASURE: We analyzed 201 clinical pregnancies in which cardiac activity had been documented by transvaginal US 35 to 42 days after ovulation in a previously infertile population treated at a tertiary fertility center. Patient age, infertility diagnosis, ovulation induction protocol, and mode of insemination were analyzed by chi 2, Fisher's exact test and logistic regression analyses. RESULTS: A profound increase in spontaneous abortion rates occurred as a function of maternal age in this population (chi 2 for trend = 15.1). A spontaneous abortion rate of 2.1% was observed for maternal ages < or = 35 years but this rate increased to 16.1% for patients > or = 36 years (odds ratio, 8.72; 95 percent confidence interval 2.3 to 32.9). A fivefold increase in spontaneous abortion rate was observed in women > or = 40 years compared with women 31 to 35 years (3.8% versus 20.0%. Infertility diagnosis, mode of insemination, and ovulation induction protocol were not associated with an increased risk of spontaneous abortion. CONCLUSIONS: The incidence of pregnancy loss after confirmation of early fetal cardiac activity by transvaginal US is substantially greater in infertile patients than previously reported, when considered as a function of maternal age. In particular, patients > or = 36 years should be counseled that their risk of spontaneous abortion is significant even after fetal heart motion is present on transvaginal US. Cautious optimism and greater surveillance may be required during the first trimester of pregnancy in these women.

The effect of varying inseminating sperm concentration in male factor and non-male factor infertility during in vitro fertilization.

OBJECTIVE: To assess the effect of varying inseminating sperm concentrations on fertilization rates and polyspermy in human in vitro fertilization (IVF). SUBJECTS AND METHODS: Eighty-six couples who completed 107 consecutive IVF cycles were assigned to one of three groups according to the results of their semen analysis (SA), sperm penetration assay (SPA), and titers of antisperm antibodies (ASA). Group 1 (non-male factor) had normal results for SA, SPA and ASA; group 2 had one abnormal result; and group 3 had two or more abnormal results. Inseminating concentrations of 50,000, 250,000, or 500,000 progressively motile sperm/oocyte were prospectively assigned to groups 1, 2 and 3, respectively. MAIN OUTCOME MEASURES: Incidence of polyspermy and fertilization rates. RESULTS: A total of 992 oocytes were available for analysis. The fertilization rate of 61% for non-male factor patient (group 1) was significantly higher than for male-factor patients [group 2 (48%) and group 3 (43%; P < .01)]. The incidence of polyspermy was 3.3%, 5.5%, and 0% for groups 1, 2 and 3, respectively, and did not differ significantly between the non-male factor and male factor groups (P = .16). Polyspermic fertilization was increased in both mature (4.1%) and postmature (5.7%) as compared to immature oocytes (1.4%; P < .05). CONCLUSION: In male factor infertile couples, increasing the inseminating concentration to 250,000 or 500,000 motile sperm/oocyte does not result in an increase in the incidence of polyspermy but does not improve fertilization rates.

The influence of supraphysiologic estradiol levels on human nidation.

OBJECTIVE: Exogenous estradiol (E2) has a well-recognized interceptive action when administered shortly after ovulation. The influence of extremely elevated levels of endogenous E2 on human oocyte fertilization and implantation are unclear. The purpose of this study was to evaluate a potential antinidatory role of extremely high endogenous E2 concentrations on implantation and pregnancy during in vitro fertilization-embryo transfer (IVF-ET). METHODS: Twenty-five patients receiving human menopausal gonadotropins (hMG) following midluteal GnRHa administration for IVF-ET, in which the maximal E2 concentration was > 5000 pg/ml (range 5358-16,344 pg/ml) were studied. Cycle parameters including oocyte and embryo characteristics, fertilization, cleavage, and implantation rates as well as pregnancy outcomes were compared to those of 25 patients treated contemporaneously whose treatment cycles had peak E2 values < 3500 pg/ml. Patients groups were matched for age, infertility diagnoses, duration of infertility and stimulation protocol. RESULTS: Cycles characterized by very high endogenous E2 levels resulted in significantly more oocytes per retrieval (21.4 +/- 1.7 versus 8.4 +/- 0.6; P < 0.0001), fewer postmature oocytes (1.6% +/- 1.0% versus 14% +/- 5.0%; P < 0.03), and a decreased fertilization rate (63% +/- 4.0% versus 73% +/- 3.0%; P < 0.04) compared to control cycles. There were no differences in the overall mean morphologic grade or cleavage rates between groups. However, high E2 cycles were associated with a significantly increased implantation rate (14% +/- 4.0% versus 8.0% +/- 4.0%; P < 0.01) and pregnancy rate per embryo transfer (62% +/- 16% versus 36% +/- 16%; P < 0.01) compared to controls. The incidence of spontaneous abortion did not differ between groups. CONCLUSIONS; Extremely high endogenous E2 levels do not appear to adversely affect implantation or overall cycle pregnancy rates in IVF-ET cycles. However, impaired fertilization rates in such cycles support a potential adverse effect on oocyte quality.

The relationship between circulating androgens, obesity, and hyperinsulinemia on serum insulin-like growth factor binding protein-1 in the polycystic ovarian syndrome.

OBJECTIVE: Our purpose was to evaluate the relationship of obesity, hyperinsulinemia, and hyperandrogenemia on serum insulin-like growth factor binding protein-1 levels in women with the polycystic ovarian syndrome. STUDY DESIGN: Insulin-like growth factor binding protein-1, insulin, and androgen levels were studied during a 3-hour intravenous glucose tolerance test in 16 women with polycystic ovarian syndrome (nine obese and seven nonobese) and 20 healthy control women (10 obese and 10 nonobese). RESULTS: Positive correlations were observed between basal (r = 0.77, p = 0.04) and area under curve (r = 0.86, p < 0.001) insulin-like growth factor binding protein-1 with basal androstenedione in the nonobese women with polycystic ovarian syndrome but not in other groups of women examined or between other androgens and insulin-like growth factor binding protein-1. An inverse relationship was observed between log area under curve insulin-like growth factor binding protein-1 levels and log body mass index in polycystic ovarian syndrome (r = -0.54, p = 0.03) and in normal women (r = -0.43, p = 0.06). The log area under curve insulin-like growth factor binding protein-1 level was approximately an inverse linear function of log area under curve insulin response for both women with polycystic ovarian syndrome (r = -0.70, p < 0.001) and control women (r = -0.72, p < 0.001). Additionally, after the area under curve insulin response during intravenous glucose tolerance testing was controlled for, the decline in area under curve insulin-like growth factor binding protein-1 responses was on average 66% less in both obese and nonobese women with polycystic ovarian syndrome compared with same-weight controls (95% confidence interval 110% to 270%, p = 0.04). CONCLUSION: These data indicate that insulin and body mass index are the major determinants of circulating insulin-like growth factor binding protein-1 and that chronic hyperandrogenemia does not appear to further reduce serum insulin-like growth factor binding protein-1 levels in obese or normal-weight women with polycystic ovarian syndrome.

Corpus luteum function and pregnancy rates with clomiphene citrate therapy: comparison of human chorionic gonadotrophin-induced versus spontaneous ovulation.

A total of 508 clomiphene citrate cycles with intra-uterine insemination (IUI) performed in 233 consecutive patients were studied. In 247 cycles insemination was performed 36-38 h after human chorionic gonadotrophin (HCG)-triggered ovulation; in the remaining 261 cycles IUI was performed 18-20 h after urinary luteinizing hormone (LH) kit detection of a spontaneous LH surge. Corpus luteum function, as determined by luteal phase length and mid-luteal progesterone concentrations, together with pregnancy rates were analysed. There was no difference in luteal phase parameters between spontaneous and HCG-triggered cycles when adjusting for patient age. Furthermore, the pregnancy rates did not differ between the HCG and LH kit groups, even after adjusting for patient age and number of motile spermatozoa inseminated. Additionally, the large numbers of cycles analysed provided sufficient power to detect increases in clinical pregnancy rates in spontaneous ovulatory cycles and HCG-induced ovulation of 10.1 and 2.4% respectively, using the customary significance level (alpha-type error) of 0.05. These findings indicate that pregnancy rates and corpus luteum function in carefully monitored clomiphene citrate/IUI cycles do not differ between HCG-triggered and spontaneous ovulatory cycles.

Insulin-like growth factors: clinical experience in ovarian function.

Insulin, insulin-like growth factor, and insulin-like growth factor binding proteins have been shown to play major roles in the modulation of both normal and disturbed ovarian physiology. Identification of many of the actions of these peptides was initially characterized using animal models. However, an increasing body of evidence has emerged to clarify their contributions in human reproductive function. It is clear that at various stages of folliculogenesis, local steroid production acts in concert with intraovarian peptides to promote dominant follicle development. This review will discuss the physiologic role(s) of the insulin-insulin-like growth factor-insulin-like growth factor binding protein family in reproductive function and disorders of androgen excess.

The influence of uterine position on pregnancy rates with in vitro fertilization-embryo transfer.

We found no difference in clinical pregnancy rates following IVF-ET in women with anteverted versus retroverted uteri. Patients can be reassured that the probability of clinical pregnancy following IVF-ET is not compromised by uterine position.

Preimplantation embryo development enhanced by epidermal growth factor.

PURPOSE: Enhanced embryo maturity and advanced stages of cleavage at the time of embryo transfer are associated with superior pregnancy rates in in vitro fertilization procedures. This study was performed to assess the potential usefulness of epidermal growth factor (EGF) to enhance the development of murine preimplantation embryos cultured in vitro. Two-cell stage mouse embryos were cultured for 72 hr with EGF at concentrations of 0.1 to 100 ng/ml. The percentage of embryos which developed to the expanded and hatching blastocyst stage at 72 hr was determined. RESULTS: The percentage of fully expanded and hatching murine blastocysts at 72 hr was significantly higher following incubation with EGF at concentrations of 2 ng/ml (44 +/- 4.1%; P < 0.02), 20 ng/ml (41 +/- 3.2%; P = 0.04), 50 ng/ml (43 +/- 2.5%; P < 0.04), and 100 ng/ml (46 +/- 3.6%; P = 0.001) compared to controls. This effect of enhanced embryonic development by EGF was neutralized by coincubation with 1.0 micrograms/ml of anti-EGF antibody. CONCLUSION: EGF at concentrations of 2 to 100 ng/ml significantly enhanced the percentage of expanded and hatching murine blastocysts at 72 hr.