J.S. Mann

Reorganization of the Endoplasmic Reticulum and Development of Ca2+ Release Mechanisms During Meiotic Maturation of Human Oocytes

Oocyte maturation in rodents is characterized by a dramatic reorganization of the endoplasmic reticulum (ER) and an increase in the ability of an oocyte to release Ca2+ in response to fertilization or inositol 1,4,5-trisphosphate (IP3). We examined if human oocytes undergo similar changes during cytoplasmic meiotic maturation both in vivo and in vitro. Immature, germinal vesicle (GV)-stage oocytes had a fine network of ER throughout the cortex and interior, whereas the ER in the in vivo-matured, metaphase II oocytes was organized in large (diameter, ∼2–3 μm) accumulations throughout the cortex and interior. Likewise, oocytes matured in vitro exhibited cortical and interior clusters with no apparent polarity in regard to the meiotic spindle. In vivo-matured oocytes contained approximately 1.5-fold the amount of IP3 receptor protein and released significantly more Ca2+ in response to IP3 compared with GV-stage oocytes; however, oocytes matured in vitro did not contain more IP3 receptor protein or release more Ca2+ in response to IP3 compared with GV-stage oocytes. These results show that at least one cytoplasmic change occurs during in vitro maturation of human oocytes that might be important for fertilization and subsequent embryonic development, but they suggest that a low developmental competence of in vitro-matured oocytes could be the result of deficiencies in the ability to release Ca2+ at fertilization.

Factors that predict the probability of a successful clinical outcome after induction of oocyte maturation with a gonadotropin-releasing hormone agonist.

OBJECTIVE To determine factors predicting cycle success after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in high-risk patients undergoing controlled ovarian stimulation with a gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist to induce oocyte maturation. DESIGN Retrospective cohort study. SETTING University-based tertiary fertility center. PATIENT(S) Women who underwent a GnRH antagonist protocol during IVF-ICSI cycles and received a GnRH agonist for oocyte maturation. INTERVENTION(S) GnRH-agonist trigger. MAIN OUTCOME MEASURE(S) Clinical and ongoing pregnancy rates and any occurrence of ovarian hyperstimulation syndrome (OHSS). RESULT(S) The serum luteinizing hormone (LH) level on the day of trigger of oocyte maturation was the single most important predictor of clinical pregnancy. Patients with a peak estradiol (E(2)) level ≥4,000 pg/mL also had statistically significant higher serum LH on the day of the GnRH-agonist trigger and had a higher clinical pregnancy rate compared with those with a peak E(2) level <4,000 pg/mL, although the two groups had comparable numbers of oocytes retrieved. No patients developed OHSS. CONCLUSION(S) Serum LH and E(2) levels ≥4,000 pg/mL on the day of the GnRH-agonist trigger are important predictors of success in patients at high risk of OHSS development. As none of the patients in this high-risk population developed OHSS, the GnRH-agonist trigger is effective in the prevention of this iatrogenic complication.

Luteal phase estradiol versus luteal phase estradiol and antagonist protocol for controlled ovarian stimulation before in vitro fertilization in poor responders

Luteal phase synchronization of follicular growth has been suggested as a means to improve ovarian response in low responders. We compared luteal E2 and antagonist (n=256) with luteal E2 only (n=57) before antagonist protocol in low responders. The addition of GnRH antagonist to luteal E2 for luteal suppression before ovarian stimulation for IVF does not improve IVF outcomes in poor responders.

Endogenous gonadotropin flare following microdose leuprolide (MDL) stimulation protocol does not correlate with in vitro fertilization (IVF) outcome

Patients undergoing first IVF cycle using MDL from October 2005 to November 2008 had serum FSH, LH, and estradiol (E2) levels measured prior to and 2 days after initiation of MDL; and evidence of a follicular flare, defined as a doubling in endogenous gonadotropins, was evaluated and correlated with clinical pregnancy, cancellation, implantation, spontaneous abortion, and ongoing pregnancy rate as well as cycle parameters. Although there was no difference in IVF outcomes, higher doses of exogeneous gonadotropins as well as greater days of stimulation were observed in patients with a documented FSH or LH flare.