GnRH antagonist does not prevent premature luteinization and ovulation in stimulated cycles with gonadotropins for IVF: two case reports

Abstract

The use of GnRH antagonists (GnRHant) is increasing in the ovarian stimulation protocol. Among several other benefits, GnRHant should prevent a premature luteinization and premature ovulation, the first described either as a 'reassuringly rare event' or 'frequent event', while the second as occurring more frequently in women with decreased ovarian reserve, advanced age and poor ovarian response. Two cases of associated premature luteinization and premature ovulation, during treatment with gonadotropins and GnRHant in IVF cycles, are here reported. In both cases, premature luteinization occurred and ovulation took place during ovarian stimulation protocols with exogenous gonadotropins and GnRHant, before reaching the criteria of hCG administration, regardless of the age of the patients and their ovarian reserve. Ovulation was documented by the disappearance of most of the developing follicles, by the transformation of endometrium from a triple line picture into a uniform hyper-echogenic image, by the presence of fluid in the pouch of Douglas, by the increase of progesterone plasma levels and the simultaneous reduction of estradiol plasma levels. This evidence can be important for a correct counseling with infertile patients in preparation for an IVF cycle.

Progestin vs. Gonadotropin-Releasing Hormone Antagonist for the Prevention of Premature Luteinizing Hormone Surges in Poor Responders Undergoing in vitro Fertilization Treatment: A Randomized Controlled Trial

“…In this trial, the LH values on the trigger day in GnRH antagonist group was lower than those in PPOS, with a bigger variance (0.40–43.18 mIU/ml), the premature LH surge occurred in 5.88% of all cases and another two cases ovulated unexpectedly before schedule. The transient LH suppression by GnRH antagonist was associated with competitive blockage of GnRH receptor, endogenous estrogen-induced GnRH release was still preserved, so that a small proportion of antagonist cycles failed to control the LH surge (26, 27). In contrast, progestin inhibits GnRH secretion on the hypothalamus if progestin is administered during the early part of the cycle before estrogen priming (28–30), the progestin administration shows an indirect, slow suppression of pituitary LH secretion, serum LH values are maintained at a relative steady level and oocyte retrieval could be easily programmed.…”

Optimal leading follicle size for final oocyte maturation in POSEIDON group 3 and 4 poor responders undergoing assisted reproductive technology cycles.

“…Hence, it may be reasonable to extend the duration of stimulation to have a larger follicular pool to obtain more viable embryos (12,21,22). However, patients with low ovarian reserve and advanced age have increased risk of premature ovulation which may lead cycle cancellation (4,11,23,24). Wu et al showed that an earlier hCG trigger when the leading follicle size was 16 mm and early oocyte retrieval prevents premature luteinization and improves the number and quality of embryos in women >43 years old (25).…”

“…Gonadotropinreleasing hormone (GnRH) antagonists are useful for women with poor response to suppress pituitary activity and prevent a premature luteinizing hormone (LH) surge during controlled ovarian stimulation (COS). However, despite GnRH antagonist administration, the occurrence of premature LH surge was reported in approximately 0.34-8.0% of the patients (2)(3)(4). Cycle management for premature ovulation involves attempting to retrieve all oocytes by aspirating the free fluid from the posterior cul-de-sac under transvaginal sonographic guidance or switching to the intrauterine insemination (IUI) protocol when all follicles are ruptured (5,6).…”

A premature luteinizing hormone surge without elevated progesterone levels has no adverse effect on cumulative live birth rate in patient undergoing a flexible GnRH antagonist protocol: a retrospective study

“…However, studies have shown that patients on the flexible protocol were more prone to a premature LH surge than those on the fixed protocol [13]. Transient LH suppression by a GnRH antagonist is achieved by competitive inhibition of the GnRH receptor, but endogenous estrogen-induced GnRH release can still occur; thus, in a small proportion of patients, antagonist cycles fail to control the LH surge [14,15]. Our study showed that the incidence of a premature LH surge without elevated progesterone levels on the flexible GnRH antagonist protocol was 12.47%.…”