The luteal phase of all stimulated in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycles is disrupted, which makes luteal phase support (LPS) mandatory. The cause of the disruption is thought to be the multifollicular development achieved during ovarian stimulation which results in supraphysiological concentrations of steroids secreted by a high number of corpora lutea during the early luteal phase. This will directly inhibit luteinizing hormone (LH) secretion by the pituitary via negative feedback at the level of the hypothalamic-pituitary axis, leading to a luteal phase defect. With the introduction of the gonadotropin-releasing hormone (GnRH) antagonist protocol, it became feasible to trigger final oocyte maturation and ovulation with a single bolus of GnRH agonist (GnRHa) as an alternative to human chorionic gonadotropin (hCG). GnRHa triggering presents several advantages, including the reduction in or even elimination of ovarian hyperstimulation syndrome. Despite the potential advantages of GnRHa triggering, previous randomized controlled trials reported a poor clinical outcome with high rates of early pregnancy losses, despite supplementation with a standard LPS in the form of progesterone and estradiol. Following these disappointing results, several studies now report a luteal phase rescue after modifications of the LPS, resulting in a reproductive outcome comparable to that seen after hCG triggering. We herein review luteal phase differences between the natural cycles, hCG trigger and GnRHa trigger and present the most recent data on handling the luteal phase after GnRHa triggering.

Background: Recently different studies suggested that discontinuation of gonadotrophin releasing hormone analogue (GnRHa) at beginning of ovarian stimulation (improvement of ovarian response to gonadotrophins) may have some benefit to poor responder patients in invitro fertilization (IVF) cycles.Objective:The efficacy of GnRHa stop protocol in poor responder patients in IVF cycles was assessed.Materials and Methods: This study was a prospective, randomized controlled trial that 40 poor responder patients (less than three mature follicles in a previous cycle) with normal basal follicle stimulating hormone (FSH) were randomly allocated into two protocols: 1) Non-stop protocol: long GnRHa suppression, and start gonadotrophins from day 3 of mense. 2) Stop-protocol: GnRHa is stopped with the onset of menses, and gonadotrophin doses remained similar to group 1.Results: A significantly higher number of follicles, oocytes, embryos and fertilization rate also shorter stimulation days and lower human menopausal gonadotropins (HMG) ampoules were recorded in the stop protocol compared to the control group. Both protocols resulted in a similar cancellation rate, pregnancy rate, estradiol level and LH level.Conclusion: Early follicular cessation of GnRHa permitted the retrieval of a significantly higher number of follicles, oocytes and embryos, and can reduce the number of HMG and stimulation days.

Background: The objective of this study was to analyze the incidence and the underlying mechanisms of empty follicle syndrome (EFS) occurring in gonadotropin releasing hormone agonist (GnRHa) triggered inin vitro fertilization (IVF) cycles with GnRH antagonist protocol in women with polycystic ovary syndrome (PCOS) of Indian origin. The study also intended to evaluate the cycle outcome following a rescue trigger.Methods: Retrospective cohort analysis of data was extracted from the hospital database of 271 PCOS patients who underwent IVF in antagonist protocol triggered with GnRHa from August 2014 to December 2016. All cases with failure to obtain oocytes following retrieval were analyzed. Continuous variables were expressed as mean±SD using t-test and Chi-squared test for categorical variables. A p<0.05 was considered statistically significant.Results: Incidence of EFS following GnRHa trigger was found to be 3.3%. False empty follicle syndrome (FEFS) accounted for majority of the cases (8.9=88.8%). Of the nine EFS, six cases were salvaged with a rescue trigger, resulted in transfer of reasonably good quality embryos in a frozen-thawed embryo replacement cycle achieving clinical pregnancy in three cases (3.6=50%).Conclusion: Our experience with EFS cases following GnRHa, albeit small, given the rarity of its occurrence, suggests that majority of EFS are of false forms and can be effectively salvaged which results in reasonably favorable outcome.

Human chorionic gonadotropin (hCG) has been used as a surrogate for the mid-cycle LH surge for several decades. Due to structural and biological similarities with LH, hCG binds to and activates the same receptor - the LH/hCG receptor. However, despite the fact that hCG effectively secures final oocyte maturation and ovulation, its use as a surrogate for LH has got several drawbacks- first and foremost a sustained luteotropic effect, facilitating ovarian hyperstimulation syndrome (OHSS).Recently GnRH antagonist protocols for the prevention of a premature LH surge were introduced, allowing final oocyte maturation to be triggered with a single bolus of a GnRH agonist (GnRHa). GnRHa is as effective as hCG for the induction of ovulation, and in addition to the LH surge a FSH surge is also induced, resembling the natural mid-cycle surge of gonadotropins. The first prospective randomized studies reported a poor clinical outcome when GnRHa was used to trigger final oocyte maturation in IVF/ICSI, due to a luteal phase deficiency, despite standard luteal phase supplementation with progesterone and estradiol.As GnRHa triggering of final oocyte maturation possesses advantages over hCG triggering in terms of a reduced, if not eliminated risk of OHSS, the retrieval of more mature oocytes, and a higher patient convenience, the challenge has been to rescue the luteal phase. The development of the present protocol for luteal phase rescue after GnRHa trigger, employing a so called modified luteal phase support will be presented. The paramount aim has been to improve pregnancy rates after GnRHa trigger without increasing the OHSS rate.Although fine tuning of the luteal phase support is still possible, GnRHa triggering is now a valid alternative to hCG trigger with potential benefits.MC questions GnRHa trigger elicits a surge of gonadotropins with duration of: 1.48 hours 2.20 hours 3.24-28 hours 4.40 hours 5.<20 hours GnRHa trigger may be used in: 1. All patients 2. PCOS patients only 3. At a smaller follicular size than HCG trigger 4. Patients transferred without a modified luteal phase support 5. All patients except the hypo/hypo patient.