Michael P. Steinkampf

Efficacy of treatment for unexplained infertility

OBJECTIVE To analyze the efficacy and cost-effectiveness of alternative treatments for unexplained infertility. DESIGN Retrospective analysis of 45 published reports. SETTING Clinical practices. PATIENT(S) Couples who met criteria for unexplained infertility. Women with Stage I or Stage II endometriosis were included. INTERVENTION(S) Observation; clomiphene citrate (CC); gonadotropins (hMG); IUI; and GIFT and IVF. MAIN OUTCOME MEASURE(S) Clinical pregnancy rate. RESULT(S) Combined pregnancy rates per initiated cycle, adjusted for study quality, were as follows: no treatment = 1.3%-4.1%; IUI = 3.8%; CC = 5.6%; CC + IUI = 8.3%; hMG = 7.7%; hMG + IUI = 17.1%; IVF = 20.7%; GIFT = 27.0%. The estimated cost per pregnancy was

Effects of epidermal growth factor and insulin-like growth factor I on the levels of mRNA encoding aromatase cytochrome P-450 of human ovarian granulosa cells

10,000 for CC + IUI,

Total testosterone assays in women with polycystic ovary syndrome: Precision and correlation with hirsutism

17,000 for hMG + IUI, and

Hormonal treatment of functional ovarian cysts: a randomized, prospective study *

50,000 for IVF. CONCLUSION(S) Clomiphene citrate + IUI is a cost-effective treatment for unexplained infertility. If this treatment fails, hMG + IUI and assisted reproduction are efficacious therapeutic options.

Multifetal reduction of high-order multiple pregnancy : comparison of obstetrical outcome with nonreduced twin gestations

The effects of growth factors to regulate the activity of aromatase, as well as the synthesis of aromatase cytochrome P-450 (P-450AROM) have been studied in human ovarian granulosa cells obtained from women undergoing oocyte retrieval. Insulin-like growth factor I (IGF-I) increased aromatase activity as well as the synthesis of P-450AROM, in a concentration-dependent fashion. The levels of hybridizable mRNA species encoding cytochrome P-450AROM were also increased with IGF-I treatment. By contrast, epidermal growth factor (EGF) had no effect on these parameters when added alone, but markedly inhibited the action of follicle-stimulating hormone (FSH) to stimulate aromatase activity, and the synthesis of cytochrome P-450AROM, as well as its ability to increase the levels of mRNA encoding the enzyme. It is concluded that these growth factors have opposite effects on aromatase activity, and that these actions reflect, in part, changes in the synthesis of cytochrome P-450AROM, which in turn are the consequence of changes in the levels of mRNA encoding this enzyme.

Effect of obesity on recombinant follicle-stimulating hormone absorption: subcutaneous versus intramuscular administration.

CONTEXT There is no standardized assay of testosterone in women. Liquid chromatography mass spectrometry (LC/MS) has been proposed as the preferable assay by an Endocrine Society Position Statement. OBJECTIVE The aim was to compare assay results from a direct RIA with two LC/MS. DESIGN AND SETTING We conducted a blinded laboratory study including masked duplicate samples at three laboratories--two academic (University of Virginia, RIA; and Mayo Clinic, LC/MS) and one commercial (Quest, LC/MS). PARTICIPANTS AND INTERVENTIONS Baseline testosterone levels from 596 women with PCOS who participated in a large, multicenter, randomized controlled infertility trial performed at academic health centers in the United States were run by varying assays, and results were compared. MAIN OUTCOME MEASURE We measured assay precision and correlation and baseline Ferriman-Gallwey hirsutism scores. RESULTS Median testosterone levels were highest with RIA. The correlations between the blinded samples that were run in duplicate were comparable. The correlation coefficient (CC) between LC/MS at Quest and Mayo was 0.83 [95% confidence interval (CI), 0.80-0.85], between RIA and LC/MS at Mayo was 0.79 (95% CI, 0.76-0.82), and between RIA and LC/MS at Quest was 0.67 (95% CI, 0.63-0.72). Interassay variation was highest at the lower levels of total testosterone (≤50 ng/dl). The CC for Quest LC/MS was significantly different from those derived from the other assays. We found similar correlations between total testosterone levels and hirsutism score with the RIA (CC=0.24), LC/MS at Mayo (CC=0.15), or Quest (CC=0.17). CONCLUSIONS A testosterone RIA is comparable to LC/MS assays. There is significant variability between LC/MS assays and poor precision with all assays at low testosterone levels.

Endometrial Shedding Effect on Conception and Live Birth in Women With Polycystic Ovary Syndrome

Estrogen (E)/progestin therapy for functional ovarian cysts is widely used in clinical practice, but the efficacy of this treatment has not been determined in controlled trials. In this study, we examined the effect of E/progestin administration in a group of infertility patients enrolled in a program of ovulation induction who had cysts identified by transvaginal sonography. Patients were randomized to receive either norethindrone 1 mg/mestranol 0.05 mg/d (group A, n = 24) or no treatment (group B, n = 24) for up to 6 weeks. Patients were re-evaluated by sonography at 3, 6, and 9 weeks after entry into the protocol. The ages, mean cyst diameters, and proportions of patients having received gonadotropins in the previous menstrual cycle were not significantly different among the two groups. All patients who had a sonographic abnormality persisting for 9 weeks were surgically explored and found to have pathological cysts. The rate of disappearance of functional ovarian cysts was not affected by E/progestin treatment.

High throughput, cell type-specific analysis of key proteins in human endometrial biopsies of women from fertile and infertile couples

OBJECTIVE To compare the obstetric outcomes of twin pregnancies obtained as a result of multifetal pregnancy reduction to those in which pregnancy reduction had not been used. DESIGN Retrospective analysis. SETTING University-based tertiary care infertility clinic. PATIENTS Seventy-four twin pregnancies continuing beyond 10 weeks. Of these, 32 gestations had undergone reduction to twins at 10 weeks. MAIN OUTCOME MEASURES Gestational age at delivery, birth weights, pregnancy complications. RESULTS All pregnancies advanced beyond 20 weeks gestation. The mean gestational age at delivery of the reduction group was 33.8 versus 35.7 weeks in the nonreduced group; only 25% of reduced pregnancies reached 37 weeks compared with 57.9% of nonreduced twins. The mean fetal birth weights of the two groups differed significantly (reduced: 2,038 g, nonreduced: 2512 g). The gestational age at delivery in patients reduced from triplets was significantly greater than in pregnancies reduced from quadruplets or higher. Multiple regression analysis revealed that for a given gestational age at delivery, a history of pregnancy reduction was associated with decreased birth weight. CONCLUSION These data suggest that multifetal pregnancy reduction does not reverse completely the decreased gestational age and impaired fetal growth associated with high-order multiple pregnancy. Furthermore, fetal growth of reduced pregnancies seems to be impaired independent of the gestational age at which delivery occurs.

The use of propofol, nitrous oxide, or isoflurane does not affect the reproductive success rate following gamete intrafallopian transfer (GIFT) - A multicenter pilot trial/survey

OBJECTIVE To determine whether recombinant follicle-stimulating hormone (rFSH) should be administered intramuscularly (i.m.) or subcutaneously (s.c.) to obese women. DESIGN Randomized, single-center, two-way crossover study. SETTING Academic clinical research center. SUBJECT(S) Nineteen healthy women of reproductive age with body mass indices of 19.9 kg/m(2)-42.8 kg/m(2). INTERVENTION(S) Leuprolide acetate 3.75 mg i.m. to achieve pituitary down-regulation as determined by serum E(2) levels. Subjects were then given a single dose of 300 IU rFSH either i.m. or s.c.. Multiple blood sampling was performed over the next two weeks, and after retreatment with leuprolide, a second 300 IU rFSH dose was given via the other administration route. MAIN OUTCOME MEASURE(S) Serum samples were analyzed in duplicate for follicle-stimulating hormone (FSH) using a standard radioimmunoassay in a single run. Maximum concentrations (C(max)), times to C(max) (T(max)), and extent of absorption (area under curve [AUC]) with i.m. vs. s.c. administration were compared using paired analysis. RESULT(S) Maximal concentrations were achieved within 24 hours with both s.c. and i.m. routes. No significant differences were found in C(max), T(max), or AUC with s.c. vs. i.m. administration. A decline of AUC occurred among subjects of higher body mass index (BMI) with rFSH given either s.c. or i.m.. Subcutaneous administration achieved AUCs comparable to i.m. administration in both normal-weight and obese subjects. CONCLUSION(S) Our data indicate that the s.c. administration of rFSH is appropriate for women regardless of body mass.

Postoperative recuperation: relation to the extent of endoscopic surgery

OBJECTIVE: To estimate whether progestin-induced endometrial shedding, before ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS). METHODS: A secondary analysis of the data from 626 women with PCOS from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed). RESULTS: Although ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live births per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; P<.001). The difference was more marked when rate was calculated per ovulation (live births per ovulation: spontaneous menses 3.0%; anovulatory with progestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; P<.001). CONCLUSION: Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared with anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin before ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS. LEVEL OF EVIDENCE: II