Howard D. McClamrock

Differences in in vitro fertilization (IVF) outcome between white and black women in an inner-city, university-based IVF program

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).

High estradiol levels and high oocyte yield are not detrimental to in vitro fertilization outcome

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.

The effect of aging on ovarian volume measurements in infertile women

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.

Endometrial Pattern on the Day of Oocyte Retrieval Is More Predictive of Implantation Success than the Pattern or Thickness on the Day of hCG Administration

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, P4on 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 DhCGwas 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.

Ovarian stimulation and intrauterine insemination at the quarter centennial: implications for the multiple births epidemic

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.

A seasonal effect on pregnancy rates in an in vitro fertilization program

A distinct seasonal effect on many reproductive processes has been previously demonstrated in both men and women. In males (1-4), alterations in both sperm quality and quantity have been observed, and directly attributed to.seasonal temperature changes in the environment. These studies revealed a significantly lower sperm count in the summer season compared to the winter season. Similarly, a potential seasonal influence on ovarian (5-7) and endometrial function (8) has also been postulated. In contrast to a temperature effect observed in men, the female reproductive axis seems particularly sensitive to the amount of daylight, also known as the light-dark effect (9). Seasonal light deprivation, characteristic of the winter months, has been associated not only with a decrease in hypothalamic-pituitary-ovarian axis function in humans but also with poor oocyte maturation in some primate species (10,11). Although the seasonality of human natural conception rates and birth rates have been well documented (9), much less is known about the reproductive outcome of assisted technologies, specifically therapeutic donor insemination and in vitro fertilization (IVF). Although several recent studies (12-

Pharmacokinetics of desogestrel

A synthetic form of desogestrel, a gonane progestin, was developed because desogestrels 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.

Ovarian hyperandrogenism: the role of and sensitivity to gonadotropins*†

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.

Polycystic ovarian syndrome and associated hirsutism in the adolescent

Abstract There is a rising interest in diagnosing polycystic ovarian syndrome in the adolescent. Menstrual irregularities, hirsutism, and acne associated with polycystic ovarian syndrome is of major concern to the adolescent female. It has also been suggested that proper diagnosis and treatment in the adolescent may prevent the development or progression into the classical adult polycystic ovarian syndrome. Despite this interest and the fact that the condition has been known for over 85 years, the etiology of polycystic ovarian syndrome remains uncertain. This review addresses the special concerns and problems of polycystic ovarian syndrome in adolescents. Androgen and hair follicle physiology are discussed. Special emphasis is placed on the various possible etiologies of polycystic ovarian syndrome as well as the associated hyperprolactinemia and hyperinsulinemia that is often seen. Careful consideration is also given to diagnosis and treatment, again with the special problems of the adolescent in mind.

Pregnancy-Related Androgen Excess

Pregnancy-related androgen excess and virilization almost always arise from conditions occurring during pregnancy. It is often stressful and challenging for the clinician because of the need for a timely diagnosis in order to estimate the likelihood of virilization of an unborn female fetus. Androgen excess in pregnancy is relatively rare; the two most common causes are gestational luteoma and hyperreactio luteinalis (theca-lutein cysts of the ovaries). Increases in androgen production in pregnant women may cause hirsutism and virilization of the mother and at times virilization of a female fetus. The risk to the fetus depends on a number of factors, including the onset of increased maternal androgen production, the severity of the increase, and the condition causing the increase. Luteoma should be suspected in women with unilateral or bilateral (47%) solid ovarian masses, whereas Krukenberg tumor remains a possibility, especially in those with bilateral lesions. The natural course of the luteoma is regression and disappearance of the lesion after delivery, and it appears that elevated cord levels of testosterone and/or androstenedione are necessary for virilization of a female fetus based on a few reported cases. Hyperreactio luteinalis should be suspected in pregnancies complicated by androgen excess with bilateral cystic ovaries noted on exam or ultrasound. This condition does not appear to put the female fetus at risk for virilization even in situations in which circulating maternal androgens are high. As with luteoma, these cysts normally regress after delivery and should not require surgical therapy. Consideration should always be given to exogenous hormone therapy in pregnancies complicated by androgen excess. Unilateral solid ovarian lesions in pregnancies complicated by androgen excess increase the risk of malignancy. Current management is mostly limited to evaluating the risk to the fetus rather than implementing intervention that may alter the course of the pregnancy.