M.R. Thomas

Clinical predictors of human blastocyst formation and pregnancy after extended embryo culture and transfer

OBJECTIVE To determine the clinical factors associated with blastocyst development and pregnancy. DESIGN Evaluation of a prospectively collected IVF database. SETTING An academic IVF practice. PATIENT(S) Couples (n = 529) undergoing their first IVF cycle who qualified for extended embryo culture (more than six zygotes) over the past 5 years. INTERVENTION(S) Seven or eight zygotes were cultured for 5 days, assessed for quality, and then transferred with excess zygotes cryopreserved at the pronuclear stage. MAIN OUTCOME MEASURE(S) Clinical predictors of blastocyst development and pregnancy. RESULT(S) The mean blastocyst development rate was 49.8%, with a median number of total and good-quality blastocysts of 4 and 2, respectively. Clinical factors that were significantly associated with good-quality blastocyst formation were younger female age, increased parity, standard insemination, and lower doses of gonadotropins. Clinical factors that were significantly associated with successful pregnancy were younger female age, higher antral follicle counts, greater numbers of total and good-/excellent-quality blastocysts, and absence of male factor infertility. CONCLUSION(S) Several clinical factors are associated with the development of good-quality blastocysts after extended embryo culture and successful pregnancy outcome. These patient and cycle characteristics may be very useful in selecting the best candidates for extended embryo culture and single blastocyst transfers, thus optimizing outcomes while reducing the risks associated with multiple pregnancies.

Transactivation of the epidermal growth factor receptor is involved in the lutropin receptor-mediated down-regulation of ovarian aromatase expression in vivo.

Ovarian follicular development and differentiation is characterized by dramatic changes in aromatase (Cyp19a1) expression. In preovulatory follicles, activation of the FSH receptor increases aromatase expression until the surge of LH decreases it. Here we provide in vivo evidence that down-regulation of Cyp19a1 by the LH surge requires efficient signaling through the epidermal growth factor receptor (EGFR). The human chorionic gonadotropin (hCG)-induced down-regulation of Cyp19a1 expression in the two different mouse models with inactivating mutations of the EGFR (wa2 and velvet) is impaired but not abolished. The hCG-induced phosphorylation of ovarian ERK1/2, expression of C/EBPbeta, and the phosphorylation of Connexin43 (two downstream targets of ERK1/2 action) are also decreased in these two mouse models. In contrast, disruption of EGFR signaling does not have any affect on the hCG-induced phosphorylation of cAMP response element-binding protein or AKT. This study provides the first in vivo evidence linking the LH receptor, the EGFR, and ERK1/2 as sequential components of a pathway that regulates ovarian Cyp19a1 expression.

What do consistently high-performing in vitro fertilization programs in the U.S. do?

OBJECTIVE To identify common clinical and laboratory practices among consistently high-performing IVF programs. DESIGN Questionnaire study of selected IVF programs. SETTING Academic and private practice IVF programs. PATIENT(S) Ten of 12 programs identified as having consistently high singleton delivery rates per cycle. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Common clinical practices. RESULT(S) Common clinical practices identified among these programs included testing all patients for ovarian reserve, endometrial defects, and hydrosalpinges; use of a mixed LH and FSH stimulation protocol with step-down dosing; and use of ultrasound guidance for ET. Common laboratory practices included selective use of intracytoplasmic sperm injection, group culture of embryos in microdrops, and use of blastocyst ET in selected cases. Common laboratory features included good air quality using filtration and heated stages for oocyte and embryo work. CONCLUSION(S) Although a number of factors were identified in this best-practices questionnaire, programs often differed in many aspects of care. However, high-performing programs cited experience of physicians, embryologists, and staff members as well as consistency of approach, attention to detail, and good communication as being vital to excellent outcomes.

Effects of exogenous testosterone supplementation in gonadotrophin stimulated cycles

BACKGROUND Various experiments suggest that ovarian follicular recruitment and growth may be increased by testosterone priming. Our aim was to determine the effects of exogenous testosterone supplementation in older women on ovarian folliculogenesis and steroidogenesis. METHODS A prospective randomized double-blind placebo-controlled crossover study was carried out. Twelve regularly menstruating non-obese women aged 38-45 years received a 12-day course of transdermal testosterone (2.5 mg per patch) or placebo patch, followed by 7 days of gonadotrophin stimulation. After at least a 1 month washout period, subjects underwent the same protocol using the opposite treatment. The main outcomes were follicular development (ultrasound measures) and hormone levels. RESULTS Following gonadotrophin stimulation, there were no differences in average number of follicles over 10 mm diameter in cycles pre-treated with testosterone versus placebo [2.10 (95% confidence interval (CI) 1.11, 3.22) versus 2.08 (95% CI 1.03, 3.14), P = 0.55]. No crossover, period (first or second test) or sequence (order of treatment) effects were noted. As expected, total and free testosterone levels were increased following testosterone treatment (312.7 +/- 122.4 versus 12.3 +/- 4.5 ng/dl and 45.5+/- 16.7 versus 1.4 +/- 0.5 ng/dl, respectively, P < 0.001) but no differences in free or total testosterone were noted by period. LH, FSH, estradiol and antral follicle counts before gonadotrophin stimulation were not altered by testosterone pretreatment or by period. CONCLUSIONS Despite increased testosterone levels, a short course of androgens had no significant effect on the number of follicles over 10 mm during stimulation with FSH in women of late reproductive age.