The Science behind 25 Years of Ovarian Stimulation for in Vitro Fertilization

Purpose The study was designed to evaluate whether cumulus cell removal 4 h post-insemination could influence fertilization and embryo quality. Methods The study included 61couples undergoing standard long down regulation protocol from July 2011 to May 2012. Sibling oocytes of each patient were randomly assigned to either the 4 h group or the 20 group. For the 4 h group, cumulus cells were removed 4 h after gamete coincubation; for the 20 group, cumulus cells removal was performed 20 h after insemination. Fertilization rate, embryo quality, pregnancy rate and implantation rate were assessed. Results A total of 801 sibling cumulus-oocyte complexes (COCs) were randomized to the 4 h group (421 COCs) or 20 h group (380 COCs). There was no difference in the two pronuclei, one pronucleus and grade 1-2 embryo rate. Three pronuclei rate was significantly higher in the 4 h group compared to the 20 h group (12.6 % vs. 8.2 %, P=0.041). Comparison of embryo transfer cycles in which either embryos from the 4 h group or 20 h group were transferred did not reveal any statistically significant differences in pregnancy or implantation rates. Conclusion The results of the present study indicate that cumulus cell removal 4 h post-insemination may increase the percentage of tripronuclear zygotes. However, normal fertilization rate, embryo development, clinical pregnancy rate and implantation rates are not influenced by the timing of cumulus cell removal.

Section: Discussionmentioning

confidence: 94%

Effect of cumulus cell removal 4 h post-insemination on fertilization and embryo quality: a prospective randomized sibling-oocyte study

Xue¹,

Jiang²,

Zhu³

et al. 2013

“…As ovarian stimulation is initiated without any control over pituitary function, a GnRH-antagonist is given as soon as the circulating estradiol rise approaches the threshold level at which endogenous LH surge may be generated. The more conventional "long" protocol, instead, is accomplished giving a GnRH-agonist from the luteal phase of the run-in cycle, and follicle recruitment is performed by exogenous gonadotropins after pituitary suppression has been achieved [17]. The "long" protocol has been the most widely used in IVF throughout the world until recent times, and has been reported to be quite effective, although prone to cause a relevant incidence of side effects and complications, such as the severe ovarian hyperstimulation syndrome (OHSS) [17].…”

Section: Discussionmentioning

confidence: 99%

MILD ovarian stimulation with GnRH-antagonist vs. long protocol with low dose FSH for non-PCO high responders undergoing IVF: a prospective, randomized study including thawing cycles

Casano

Guidetti²,

Patriarca

et al. 2012

Objective To compare the effectiveness of two stimulation protocols in non-polycystic ovary (PCO) high responders undergoing in vitro fertilization (IVF). Design Prospective randomized trial. Setting A Reproductive Medicine and IVF Unit of a University Hospital and a private IVF Clinic. Methods Four hundred-and-twelve normoovulatory women with good ovarian responsiveness were randomized to receive either the "mild" (FSH 150 IU/day from day 4 of a spontaneous cycle followed by GnRH-antagonist from day 8; n=205) or the "long" (FSH 150 IU/day; n=207) stimulation protocol. The outcome of these two regimens was compared including "fresh" and thawing cycles. Results The total FSH dose and the peak estradiol level were significantly lower in the "mild" protocol, whereas the retrieved oocytes, fertilization rate, number and quality of embryos, pregnancy and implantation rates, cumulative "fresh plus thaw" success rate, and incidence of severe ovarian hyperstimulation syndrome were comparable with the two regimens. Conclusions In young, normoovulatory patients with good ovarian responsiveness undergoing IVF the "mild" stimulation protocol has effectiveness and risks comparable to the "long" protocol with low FSH starting dose, even when thawing cycles are included in the comparison.

“…The so-called "mild" protocols (1), in which exogenous gonadotropins are started some days after the beginning of the cycle, allow initial follicle recruitment by endogenous FSH (21,22). Compared to the "classical" COS regimens, they show a lower follicular recruitment, and were repeatedly shown to lead to a lower oocyte yield (23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of late-start Corifollitropin-alfa administration for controlled ovarian hyperstimulation in IVF: a cohort, case–control study

Revelli

Pittatore

Casano

et al. 2015

Objective To investigate efficacy and safety of a controlled ovarian stimulation (COS) protocol in which a single dose of Corifollitropin-alfa (CFα) was administered on day 4 of a GnRH-antagonist cycle. Design Cohort case-control study. Setting University Hospital. Patients One hundred twenty-two normally cycling women expected to be normal responders to COS. Interventions In 61 patients, CFα (100-150 μg) was injected subcutaneously on day 4 of a spontaneous menstrual cycle; a GnRH-antagonist was added from day 8 (fixed protocol; 0.25 mg/day). If needed to complete follicular maturation, recombinant FSH (rFSH) daily injections (150/200 IU/day) were given from day 11. A control group of 61 matched women was stimulated with daily subcutaneous injections of rFSH (100-150 U/day) from day 4 of the cycle, and received GnRH-antagonist (0.25 mg/day) from day 8. IVF or ICSI was performed according to the sperm characteristics, and 1-2 embryos were transferred in utero under US guidance on day 2.Main outcome measures Number of retrieved cumulusoocyte complexes (COCs), clinical pregnancy rate (PR), implantation rate (IR), ongoing PR at 10 weeks, number of injections/cycle, ovarian hyperstimulation syndrome (OHSS) rate.Results No cycle was cancelled and the mean number of retrieved COCs was comparable in patients and controls. About 60 % of CF-alfa treated women had no need of daily rFSH addition, and the mean number of injections/cycle was significantly lower in the CF-alfa group than in controls (p<0.05). The ongoing PR/transfer was 36.8 % in CF-alfa group and 37.5 % in controls. No patient developed severe OHSS, and the incidence of moderate OHSS was similar in cases and controls. Conclusions CFα may be started on day 4 of the cycle obtaining results comparable to those of a COS using day 4-start daily rFSH, with significantly less injections and a similar risk of OHSS.