Association between growth dynamics, morphological parameters, the chromosomal status of the blastocysts, and clinical outcomes in IVF PGS cycles with single embryo transfer.

PURPOSE: The purpose of the present study is to examine interconnection between speed of embryo development, the genetic status of the blastocysts, and clinical outcomes in IVF preimplantation genetic screening (PGS) cycles with single embryo transfer (SET). METHODS: The retrospective comparative study has been performed between January 2013 and January 2016. Seven hundred thirty-seven cycles of IVF treatment with PGS, followed by 503 SETs, were included in the study. Normally fertilized oocytes were hatched on day 3, were cultured to the blastocyst stage, and were biopsied only when at least three to seven cells were herniating from zona pellucida on the morning of day 5 (≤118 h) or day 6 (≥139 h). A total of 3705 embryos were analyzed for euploidy rates and blastocyst morphology. All embryos were vitrified after the biopsy, and selected embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. RESULTS: The euploidy rate was significantly higher among embryos biopsied on day 5 versus day 6: 59.44 ± 4.1 and 48.19 ± 3.8, respectively, p < 0.05. The difference in euploidy rates between embryos biopsied on day 5 versus day 6 in matched age groups increased from 5.83 to 25.46% with advancing maternal age. Our data demonstrated no statistically significant difference in euploidy rates between good-quality embryos biopsied on day 5 in the group of patients <38 years old and embryos in PGS cycles using donor oocytes: 71.12% (336/472) and 75.68% (221/292), respectively, p = 0.174, χ 2 = 1.848. In 270 out of 503 SETs, transferred embryos were biopsied on day 5 (ongoing pregnancy rate was 64.6% in a group of patients <38 years old, and in a group of patients ≥38 years old, ongoing PR was 64.2%). In 233 out of 503 cycles, transferred embryos were biopsied on day 6 (ongoing PR was 46.6% in a group of patients <38 years old, and in a group of patients ≥38 years old, ongoing PR was 50.8%). In all study groups, the ongoing pregnancy rate was higher when the transferred embryo was available for biopsy on day 5. CONCLUSIONS: Good- and fair-quality embryos available for biopsy on day 5 have higher euploidy rates and have a higher chance to result in an ongoing pregnancy. Euploidy rate has significant variations within the same age group depending on the morphology of the blastocysts.

Comparison of inhibin B and estradiol responses to intravenous FSH in women with polycystic ovary syndrome and normal women.

BACKGROUND: Inhibin B (Inh B) is produced by pre-antral and early antral follicles whereas estradiol (E(2)) is a product of follicles undergoing antrum formation. This temporal distinction is evident in the patterns of Inh B and E(2) release earlier and later during the follicular phase of the menstrual cycle, respectively. However, in previous studies of women with polycystic ovary syndrome (PCOS) and normal controls, release of these granulosa cell (GC) products appears to be simultaneous in response to FSH stimulation. In order to reconcile these disparate findings, we conducted dose-response studies in both PCOS women and normal controls to determine whether GC product responses were due to the amount of FSH administered. In addition, we compared FSH-stimulated responses in PCOS women at various stages of recovery following ovarian suppression with a long-acting GnRH agonist to examine whether Inh B and E(2) responses reflected the level of ovarian follicle activity (i.e. circulating E(2) levels). METHODS: Women with PCOS, 18-35 years (n = 23), and normal ovulatory controls, 18-35 years (n = 10) were recruited for study. Dose-responses were assessed over 24 h following intravenous administration of 0 (saline), 37.5, 75 and 150 IU of recombinant human FSH (r-hFSH) in PCOS and normal women. In addition, E(2) and Inh B responses to 150 IU of r-hFSH were assessed at baseline and 4, 6 and 8 weeks following suppression of ovarian steroidogenesis by a long-acting GnRH agonist in PCOS women. RESULTS: In PCOS women and normal controls, serum Inh B and E(2) exhibit similar and simultaneous dose-responsiveness to FSH stimulation. During recovery from ovarian suppression, basal and stimulated Inh B release appear to be restored earlier than that of E(2) in PCOS women. CONCLUSIONS: These findings are consistent with the notion that, in PCOS women, the level of ovarian follicle activity largely determines the earlier release of Inh B compared with E(2).

Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome.

CONTEXT: In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. OBJECTIVE: The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. DESIGN: A prospective study was conducted to compare androgen production in response to FSH in two groups of women. SETTING: The study was conducted in a General Clinical Research Center in a tertiary academic medical center. PATIENTS: Women with PCOS, 18-35 yr (n = 20), and normal ovulatory controls, 18-35 yr (n = 10), were recruited for study. INTERVENTIONS: Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). MAIN OUTCOME MEASURES: The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. RESULTS: Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. CONCLUSIONS: These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.

Serum anti-mullerian hormone concentrations are not altered by acute administration of follicle stimulating hormone in polycystic ovary syndrome and normal women.

CONTEXT: In the human ovary, expression of anti-Mullerian hormone (AMH) is detected primarily in granulosa cells of preantral and small antral follicles. This finding is consistent with the tight correlation between circulating AMH levels and the number of small antral follicles (2-5 mm) in normal and polycystic ovary syndrome (PCOS) women. In addition, the greater follicle count in PCOS is mirrored by significantly higher serum AMH levels compared with those of normal women. Despite the utility of AMH measurements in evaluating ovarian physiology and function, the regulation of AMH remains poorly understood. OBJECTIVE: The objective was to determine whether gonadotropins acutely regulate serum AMH in women with PCOS and normal women. DESIGN: We conducted a prospective study to compare ovarian responses to FSH in two groups of women. SETTING: The study was conducted in a General Clinical Research Center in a tertiary academic medical center. PATIENTS: Women with PCOS (age, 18-35 yr; n = 16) and normal ovulatory controls (age, 18-35 yr; n = 11) were recruited for study. INTERVENTIONS: Serum samples were measured over a 24-h period after an iv injection of recombinant human FSH (150 IU). MAIN OUTCOME MEASURE(S): Serum AMH responses after FSH administration were measured. RESULTS: Basal serum AMH levels were markedly increased in women with PCOS compared with levels observed in normal women. After FSH injection, PCOS women failed to demonstrate changes in circulating AMH over 24 h. A similar lack of alteration in serum AMH was observed in normal women. CONCLUSIONS: These findings suggest that in PCOS and normal women, acute exposure to FSH does not appear to exert an effect on AMH production.

Comparison of follicle-stimulating-hormone-stimulated dimeric inhibin and estradiol responses as indicators of granulosa cell function in polycystic ovary syndrome and normal women.

CONTEXT: Follicular phase secretion of inhibin B, like that of estradiol (E(2)), correlates with the quantity and quality of developing follicles. However, it has not been established whether inhibin B responses to gonadotropin stimulation parallel those of E(2) as a reflection of granulosa cell functional capacity. OBJECTIVE: Our objective was to determine whether inhibin B responses to FSH stimulation are similar to those of E(2) in women with polycystic ovary syndrome (PCOS) and normal women. DESIGN AND SETTING: We conducted a prospective study to compare ovarian responses in two groups of women at a general clinical research center in a tertiary academic medical center. PATIENTS: Women with PCOS, 18-35 yr (n = 19), and normal ovulatory controls, 18-35 yr (n = 7), were recruited for study. INTERVENTIONS: Serum samples were measured over a 24-h period after an iv injection of recombinant human FSH, 150 IU. MAIN OUTCOME MEASURES: Serum E(2), inhibin A, and inhibin B responses after FSH administration were assessed. RESULTS: In PCOS women, the 24-h production of inhibin B and E(2) after FSH was significantly greater than that of normal controls. Within the PCOS group, the fold change in inhibin B was significantly greater than that of E(2). Inhibin A responses between groups were similar and of markedly lower magnitude. CONCLUSIONS: FSH-stimulated inhibin B responses may be employed to assess the functional capacity of granulosa cells in PCOS and normal women.