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The measurement of ovarian volume has been recently shown to predict follicular response in in-vitro fertilization (IVF), specifically a lower number of retrieved oocytes with decreasing ovarian volume. This test appears to be better than basal follicle-stimulating hormone (FSH) as a prognostic measure of ovarian reserve. However, the effect of pituitary desensitization on ovarian volume has not been previously investigated. We prospectively evaluated 38 women undergoing IVF using a long luteal leuprolide acetate (LA) protocol. All women had their ovarian volume measurements performed on day 21, the day of LA start, and again on the day of gonadotrophin start. The mean age was 30.6 ± 3.9 years (range 23-37). Basal FSH was 5.4 ± 1.9 IU/l (range 1.2-10.2). The mean preLA ovarian volume was 7.0 ± 3.6 cm3 (left ovary 6.8 ± 3.9, right ovary 7.1 ± 3.8), compared to 6.3 ± 4.2 cm3 postLA (left ovary 6.0 ± 4.9, right ovary 6.5 ± 4.8) (not significant). The mean number of small antral follicles noted in both ovaries was also unchanged after pituitary desensitization. Pituitary desensitization using LA had no effect on overall ovarian volume measurements. The total number of retrieved oocytes decreased with increasing age and decreasing ovarian volume. [ABSTRACT FROM PUBLISHER]

Ovarian stimulation and intrauterine insemination (OS/IUI), a mainstay of current infertility therapy and a common antecedent to IVF, is a significant driver of the multiple births epidemic. Redress of this challenge, now marking its quarter centennial, will require a rethinking of current practice patterns. Herein we explore prospects for prevention, mitigation, and eventual resolution. We conclude that the multiple births attributable to OS/IUI may not be entirely preventable but that the outlook for their mitigation is promising, if in need of solidification. Specifically, we observe that low-dose (≤ 75 IU) gondotropin, clomiphene, and especially off-label letrozole regimens outperform high-dose (≥ 150 IU) gonadotropin counterparts in the gestational plurality category while maintaining comparable per-cycle pregnancy rates. Accordingly we recommend that, subject to appropriate exceptions, high-dose gonadotropin regimens be used sparingly and that whenever possible they be replaced with emerging alternatives. Finally, we posit that OS/IUI is not likely to be superseded by IVF absent further commoditization and thus greater affordability., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

There is an increasing body of evidence that excess weight is associated with decreased pregnancy rates, lower birth rates, lower implantation rates, and the possibility of decreased follicle development and oocyte numbers as well as an increased gonadotropin requirement in patients undergoing in vitro fertilization or intracytoplasmic sperm injection. Whether the mechanism is ovarian, endometrial, or a combination of the two is unknown.

Purpose: Few studies have addressed the effect of weight on IVF outcome, with some showing a decrease in IVF success and some showing no change in overweight women (BMI > 25 kg/m2) compared to women with normal weight (BMI < 25 kg/m2)., Methods: One hundred thirty-nine women < 40 years old undergoing 180 IVF cycles with fresh embryo transfers were retrospectively evaluated between January 1997 and March 1999, stratified by body mass index (BMI) (cutoff of 25)., Results: In the group with BMI > 25 kg/m2, basal FSH, implantation rates (IR), and pregnancy rates (PR) were significantly lower, while the duration of stimulation, gonadotropin requirements, and spontaneous miscarriages were slightly higher, compared to the BMI < or = 25 group., Conclusions: Excess weight defined as BMI > 25 kg/m2 has a negative impact on IVF outcome. Future prospective studies evaluating oocyte and/or embryo quality, and androgen and insulin levels, between overweight women and those with normal weight are needed.

Ovarian volume measurements have been recently shown to be predictive of response to ovarian stimulation. Women with small ovarian volumes, i.e. <3 cm(3), have a higher incidence of cycle cancellation, together with a lower peak oestradiol concentration, lower number of retrieved oocytes, and lower pregnancy rates, compared with women with larger ovarian volumes. We prospectively investigated whether a higher dose, microdose flare gonadotrophin-releasing hormone (GnRH) agonist protocol, can improve IVF outcome in women with a small ovarian volume. Only the first IVF cycle was reviewed. In total, 109 women aged <40 years undergoing 109 cycles were prospectively evaluated. Women with an ovarian volume of < or =3 cm(3) noted on the day of luteal GnRH agonist administration had their stimulation regimen changed to a more aggressive microdose flare GnRH agonist protocol. In all, 30 women (27.5%) with an ovarian volume of <3 cm(3), and 79 women (72.5%) with an ovarian volume of >3 cm(3) were compared. Women with an ovarian volume of <3 cm(3) had a significantly higher incidence of unexplained infertility as their presenting aetiology, compared with women with a larger ovarian volume (33 and 8.6%, P = 0.0036). There was a significant negative correlation between age and ovarian volume, and between day 3 FSH concentration and ovarian volume. We also report a significant positive correlation between body mass index and ovarian volume. There was also a significant positive correlation between ovarian volume and the number of oocytes retrieved. Despite a trend towards higher day 3 FSH concentrations, a significantly longer duration of stimulation, higher gonadotrophin requirements, and lower oocyte yield, the implantation and pregnancy rates were comparable between the two groups. Women with a small ovarian volume noted at baseline ultrasound can have comparable implantation and pregnancy rates to those with larger ovarian volumes with the use of a higher dose gonadotrophin, microdose GnRH agonist stimulation.

Objective: To compare IVF outcomes between white and black women in an inner-city, university-based IVF program., Design: Retrospective study., Setting: University-based IVF program., Patient(s): Ninety-five white women undergoing 121 cycles and 37 black women undergoing 47 cycles., Intervention(s): None., Main Outcome Measure(s): Implantation rate and pregnancy rate (PR)., Result(s): Black women constituted 28. 0% of the population and underwent 28.0% of the total cycles. There were no statistically significant differences in age, basal FSH, number of ampules, duration of stimulation, endometrial thickness, P on the day of hCG, cancellation rate, number of oocytes, or embryos transferred. However, the duration of infertility, body mass index (BMI), incidence of tubal-factor infertility, and peak E(2) levels were significantly higher in black women. In addition, a larger proportion of black women required aggressive stimulation than white women (70.2% and 43.0%). Both implantation rates and clinical PRs were significantly lower in black women than in white women (9.8% and 19.2% compared with 23.4% and 42.2%, respectively)., Conclusion(s): Black women have poorer IVF outcomes than white women. These differences can be partly explained by higher BMI, longer duration of infertility, higher incidence of tubal-factor infertility, and higher peak E(2).

Purpose: Multiple studies have confirmed a lower implantation (IR) and pregnancy rate (PR) in women who exhibit a homogeneous pattern (pattern II) of the endometrium compared to a triple-line pattern (pattern I) on the day of hCG administration. However, no data are available to evaluate if patients alter their endometrial thickness and pattern between the day of hCG administration (DhCG) and the day of oocyte retrieval (DRET) and whether these changes adversely affect endometrial receptivity., Methods: We prospectively evaluated 86 women (mean age, 32.9 +/- 3.8 years; range, 24-40 years) undergoing 103 IVF/ET cycles., Results: Pattern II was noted in 7 cycles (6.8%) on DhCG, compared to 96 cycles with pattern I (93.2%). However, 20 cycles (19.4%) had pattern II on DRET. The ongoing IR was 13.0% (3/23) in the pattern II group compared to 20.8% (76/365) in the pattern I group on DhCG (P = NS). However, a significant decrease in the ongoing IR, to 9.9% (7/71), was noted in pattern II, compared to 23.3% (71/305) in pattern I, on DRET (P = 0.019). There was no difference in age, basal FSH, peak E2, P4 on the day of hCG, number of oocytes, number of ET, or endometrial thickness between pregnant and nonpregnant patients, or between patients with pattern I and those with pattern II. A trend toward higher progesterone levels on DhCG was noted in women with pattern II (P = 0.078)., Conclusions: Endometrial pattern, rather than thickness, on the day of oocyte retrieval appears to be an important prognosticator of endometrial receptivity.

The role of luteal oestradiol for successful implantation in humans seems to be permissive rather than obligatory. Few studies have attempted to clarify the role of early luteal oestradiol in in-vitro fertilization (IVF) outcome, whether peri-implantation oestradiol is predictive of successful IVF outcome. We retrospectively analysed 106 women undergoing 106 IVF/embryo transfer cycles. Only the first treatment cycle per patient was analysed. Peak oestradiol denoted the concentration on the day of human chorionic gonadotrophin (HCG) administration. Mid-luteal oestradiol was obtained 3 days after embryo transfer (8 days after HCG administration). A total of 44 pregnancies were noted (41.51%). There were no differences in age, cycle day 3 follicle stimulating hormone (FSH), peak oestradiol, number of retrieved oocytes, number of embryo transfers, and mid-luteal oestradiol between pregnant and non-pregnant women. However, the ratio of day of HCG oestradiol to mid-luteal oestradiol was highly predictive of successful outcome: the ongoing pregnancy rate and implantation rate (sacs with fetal heart beat/embryo transfer) were 15.8 and 5.7% respectively if the above ratio exceeded 5.0 (n = 19), compared to 42.1 and 16.3%, and 53.3 and 26. 5% if the ratio was between 0.4 and 2.5 (n = 57), and between 2.5 and 5.0 (n = 30) respectively. Our study suggests that the magnitude of decline in oestradiol concentrations after oocyte retrieval may be important in predicting IVF success. We postulate that endometrial integrity may become compromised when a dramatic drop in oestradiol occurs by the mid-luteal period. Whether these women benefit from oestradiol supplementation after oocyte retrieval remains to be investigated.

Objective: To evaluate the impact of elevated peak E2 levels and a high number of retrieved oocytes on implantation in patients undergoing assisted reproductive techniques., Design: Retrospective study., Setting: University-based IVF program., Patient(s): One hundred six patients undergoing 106 IVF cycles. High responders were defined as those who had peak E2 levels of >3,000 pg/mL on the day of hCG administration (n = 38) or >15 retrieved oocytes (n = 48). Their IVF outcomes were compared with those of patients whose peak E2 levels were < or =3,000 pg/mL (n = 68) or who had < or =15 retrieved oocytes (n = 58)., Intervention(s): None., Main Outcome Measure(s): Implantation and pregnancy rates., Result(s): There were no statistically significant differences in age, basal FSH level, basal E2 level, number of ampules of gonadotropins required, fertilization rate, number of ETs, implantation rate, or pregnancy rate between normal and high responders or between women who did and did not become pregnant. In addition, no differences were detected when outcome was analyzed according to the stimulation regimen used., Conclusion(s): Elevated peak E2 levels and high oocyte yield are not detrimental to IVF outcome. More studies are needed to characterize the threshold E2 levels above which implantation rates are reduced.

Objective: To test the hypothesis that aging is associated with a decrease in ovarian volume, and that the FSH level and volume are correlated inversely., Methods: One hundred nine women who had 73 in vitro fertilization cycles and 36 ovulation induction cycles were analyzed. Basal FSH and estradiol (E2) levels were measured on cycle day 3, and ovarian volume was measured and antral follicles were counted on the day of starting gonadotropin., Results: The mean age (+/- standard deviation) was 32.6+/-4.7 years. The mean FSH was 6.9+/-2.4 IU/L. The mean ovarian volume was 6.0+/-4.7 cm3. There were no significant differences between the median volumes of the left and right ovaries in individual subjects (4.6 and 4.8 cm3, respectively; interquartile range 3.0-7.3 and 3.1-7.9; P = .79). There was a significant positive correlation between age and FSH level (R = .372, P<.001), but not between age and ovarian volume (R = .039, P = .69). A significant relation was noted between FSH and the number of follicles (H = 20.8, P<.001), but not between FSH and volume (R = .102, P = .29). There was a significant decrease in the number of follicles and a higher cycle cancellation rate in women with volume smaller than 3 cm3 compared with those with volume greater than 3 cm3., Conclusion: Women with small ovarian volumes, low number of antral follicles, and normal basal FSH and E2 levels may have diminished ovarian reserve.

The impact of hydrosalpinx (HSPX) on in-vitro fertilization (IVF) outcome has recently been the subject of intense debate. Most, but not all, studies have reported decreased implantation and pregnancy rates and increased early pregnancy loss in HSPX patients. This has led to prophylactic salpingectomies prior to IVF in HSPX patients despite the lack of any prospective studies to suggest that any improvement will occur. Women with HSPX constitute a heterogeneous population because some conceive easily with IVF while others do not until after surgical correction. HSPX also increases in size with ovarian stimulation, and can cause implantation failure by fluid reflux into the uterine cavity. Careful assessment of the endometrial lining is mandatory in HSPX to rule out fluid reflux from the HSPX. We present two case reports of patients whose HSPX enlarged with ovarian stimulation, causing fluid reflux into the uterine cavity which was only noted after human chorionic gonadotrophin (HCG) administration.

Background: Cervical pregnancy can be a life-threatening entity, with the diagnosis often made on the hysterectomy specimen. A case of distal ectopic pregnancy involved the endocervical canal, and prompt diagnosis and treatment allowed the preservation of fertility., Case: The patient presented at six weeks' gestation with vaginal bleeding. Serial ultrasound examinations revealed a viable pregnancy and ultimately suggested placental implantation within the endocervical canal. Curettage was performed using cervical stay sutures at the three and nine o'clock positions, with minimal bleeding and no postoperative morbidity. One year after the procedure the patient had a spontaneous delivery of a full-term male following an unremarkable prenatal course., Conclusion: Improvements in sonography and serum testing have allowed earlier diagnosis and hence greater success with conservative management of cervical pregnancy.

A synthetic form of desogestrel, a gonane progestin, was developed because desogestrel's enhanced selectivity eliminates adverse, androgen-dependent, metabolic effects at contraceptive doses. Desogestrel is rapidly and completely metabolized in the liver and gut wall to 3-keto-desogestrel, which is the active metabolite mediating the progestin effects. Because of its unique 11-methylene side chain, desogestrel cannot be metabolized to any other known progestin, nor is desogestrel a naturally occurring metabolite of any other progestin. The pharmacokinetic parameters of 3-keto-desogestrel are generally comparable with those of levonorgestrel and norethindrone. Therefore any differences in pharmacologic activities must be attributed to differences in intrinsic activities. Unlike gestodene, 3-keto-desogestrel has a lower affinity for sex hormone-binding globulin, which results in markedly lower plasma levels after administration. After oral administration of 150 micrograms of desogestrel, plasma levels are less than half the levels of gestodene after an oral dose of 75 micrograms.

The occurrence of pregnancy in the face of untreated Cushing syndrome is rare because of the high incidence of ovulatory disturbances experienced by patients with the disorder. A total of 58 patients with 65 pregnancies has been reported in the literature to date. Although pituitary-dependent adrenal hyperplasia is the most common etiology of Cushing syndrome in the general population, adrenal adenoma is more common in the pregnant population. Significant maternal morbidity is attributable to hypertension, congestive heart failure, and poor tissue healing. Prematurity and intrauterine growth retardation account for most of the perinatal morbidity; perinatal mortality is substantial. Treatment directed at relieving hypercortisolism has been instituted during pregnancy: Pituitary or adrenal surgery, chemotherapy, and pituitary irradiation have all been reported, with variable results. Information is lacking on any alteration of maternal morbidity after treatment. The impact of therapy on perinatal outcome appears limited to a reduction in the prematurity rate, but overall numbers are small and such a conclusion should be viewed with caution. No significant maternal or perinatal complications secondary to treatment itself were reported.

A case of Cushing's syndrome caused by an adrenal adenoma seen at 10 weeks' gestation is described. The pregnancy was terminated at 18 weeks' gestation, representing the first reported case of therapeutic termination of pregnancy in Cushing's syndrome with prostaglandin E2 vaginal suppositories.

To determine if ovarian hyperandrogenism represents enhanced gonadotropic stimulation, augmented ovarian sensitivity to gonadotropins, or both, we have undertaken to evaluate (1) the 24-hour integrated concentrations of serum total testosterone (T) and luteinizing hormone (LH) and (2) the ovarian response of T to exogenous gonadotropic stimulation. To this end, two groups of women, hyperandrogenic anovulatory (n = 4) and early follicular phase (n = 4) normally-cycling controls, were subjected to continuous blood withdrawal over 24 hours with a portable Cormed pump (Cormed Inc., Middleport, NY) and to exogenous stimulation with human chorionic gonadotropin. Our current observations support the notion that ovarian hyperandrogenism represents the combined impact of an overall increase in gonadotropic support coupled with augmented ovarian sensitivity to gonadotropic stimulation.

Extracts of amniocentesis samples from 144 women were tested for the presence of mutagenic substances using tester strain TA1538 in the Ames Salmonella/mammalian-microsome mutagenicity test. Because the volume of amniotic fluid in these samples was limited (generally less than 10 ml), we investigated modifications of this mutagenesis assay that could increase its ability to detect effects from small quantities of test material. Using mutagenicity in samples of urine from smokers as a model, it appeared that improved ability to detect small amounts of mutagen could be obtained by reducing volumes of media and reagents while keeping the amount of test sample constant. This modification resulted in a test procedure capable of readily detecting mutagenicity in volumes of urine from smokers that were smaller than the volumes of amniotic fluid available. Tests of amniotic fluid extracts by this modified procedure showed small increases in revertants, about 50% above dimethylsulfoxide solvent control values. Results of procedures to control for technical factors possibly contributing to these increases suggested that the increased values could not be readily explained by contamination of test samples with mutagens during the extraction procedure. They also were not explained by alterations in spontaneous numbers of revertants associated with changes in the density of bacterial lawn growth. The increases suggest the presence of small amounts of mutagenic material in many of the amniotic fluid samples. At the doses employed, mutagenic activity in these samples was not associated with maternal smoking.