GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles—A Systematic PRISMA Review and Meta-analysis

IntroductionThe use of GnRH agonist (GnRHa) for final oocyte maturation trigger in oocyte donation and elective frozen embryo transfer cycles is well established due to lower ovarian hyperstimulation syndrome (OHSS) rates as compared to hCG trigger. A recent Cochrane meta-analysis concluded that GnRHa trigger was associated with reduced live birth rates (LBRs) in fresh autologous IVF cycles compared to hCG trigger. However, the evidence is not unequivocal, and recent trials have found encouraging reproductive outcomes among couples undergoing GnRHa trigger and individualized luteal LH activity support. Thus, the aim was to compare GnRHa trigger followed by luteal LH activity support with hCG trigger in IVF patients undergoing fresh embryo transfer.Material and methodsWe conducted a systematic review and meta-analysis of randomized trials published until December 14, 2016. The population was infertile patients submitted to IVF/ICSI cycles with GnRH antagonist cotreatment who underwent fresh embryo transfer. The intervention was GnRHa trigger followed by LH activity luteal phase support (LPS). The comparator was hCG trigger followed by a standard LPS. The critical outcome measures were LBR and OHSS rate. The secondary outcome measures were number of oocytes retrieved, clinical and ongoing pregnancy rates, and miscarriage rates.ResultsA total of five studies met the selection criteria comprising a total of 859 patients. The LBR was not significantly different between the GnRHa and hCG trigger groups (OR 0.84, 95% CI 0.62, 1.14). OHSS was reported in a total of 4/413 cases in the GnRHa group compared to 7/413 in the hCG group (OR 0.48, 95% CI 0.15, 1.60). We observed a slight, but non-significant increase in miscarriage rate in the GnRHa triggered group compared to the hCG group (OR 1.85; 95% CI 0.97, 3.54).ConclusionGnRHa trigger with LH activity LPS resulted in comparable LBRs compared to hCG trigger. The most recent trials reported LBRs close to unity indicating that individualization of the LH activity LPS improved the luteal phase deficiency reported in the first GnRHa trigger studies. However, LPS optimization is needed to further limit OHSS in the subgroup of normoresponder patients (<14 follicles ≥ 11 mm).Prospero registration numberCRD4201605109

GnRHa trigger—the story of the ugly duckling

The objective of this invited review is to describe the introduction and development of the GnRH agonist (GnRHa) trigger protocol in modern in vitro fertilization, focusing on ovarian hyperstimulation syndrome (OHSS) prevention and, equally important on the role of GnRHa trigger as an opener of the luteal phase “black box.”The GnRHa trigger and freezing of all embryos is the ultimate weapon against OHSS in the OHSS-risk patient. In the non OHSS-risk patient, GnRHa trigger followed by a modified luteal phase support with lutein hormone activity and subsequent fresh embryo transfer results in excellent reproductive outcomes. Thus, the GnRHa trigger has paved the way for a virtually OHSS-free clinic, and equally important is the fact that the early lessons learned from studying the GnRHa trigger opened the “black box” of the luteal phase enabling improved reproductive outcomes in both fresh and frozen embryo transfer cycles

Individualized controlled ovarian stimulation in expected poor-responders: an update

Abstract Controlled ovarian stimulation with subsequent multi-follicular development continues to be a keystone in ART. Evidence supports an individualized approach to ovarian stimulation, usually involving combinations of ovarian reserve tests, body mass index and age to tailor the exogenous gonadotropin dose, and potentially adjuvant treatment aiming for high safety and a shortening of time to live birth. While stimulation and trigger concepts have been developed successfully in normo- and hyperresponder patients, the poor responder patient remains difficult to manage. However, recent advances in definition and classification of the expected poor ovarian responder patient might enable a more accurate and clinically useful interpretation of new treatment concepts in a more homogenous study population. In the present review, we discuss the classification of the expected poor ovarian responder patient as well as clinically useful measurements of efficacy for controlled ovarian stimulation, and finally, we discuss the evidence for clinical management of patients with expected poor ovarian response, including adjuvant treatments such as growth hormone, androgens, and LH activity. In conclusion, the best available evidence supports that the treatment of the expected poor ovarian response patient should be individualized in all steps of ART, including the choice of GnRH analogue, the gonadotropin type and dose, ovulation trigger, and the possible use of adjuvant therapies

Lactobacilli and Their Probiotic Effects in the Vagina of Reproductive Age Women

In the present narrative review, the probiotic effects of vaginal Lactobacillus spp. are described in detail, covering the importance of the differential production of lactic acid, the lactic acid D/L isoforms, the questionable in vivo effect of hydrogen peroxide, as well as bacteriocins and other core proteins produced by vaginal Lactobacillus spp. Moreover, the microbe–host interaction is explained with emphasis on the vaginal mucosa. To understand the crucial role of Lactobacillus spp. dominance in the vaginal microbiota, different dysbiotic states of the vagina are explained including bacterial vaginosis and aerobic vaginitis. Finally, this review takes on the therapeutic aspect of live lactobacilli in the context of bacterial vaginosis. Until recently, there was very low-quality evidence to suggest that any probiotic might aid in reducing vaginal infections or dysbiosis. Therefore, clinical usage or over the counter usage of probiotics was not recommended. However, recent progress has been made, moving from probiotics that are typically regulated as food supplements to so-called live biotherapeutic products that are regulated as medical drugs. Thus, recently, a phase 2b trial using a Lactobacillus crispatus strain as a therapeutic add-on to standard metronidazole showed significant reduction in the recurrence of bacterial vaginosis by 12 weeks compared to placebo. This may constitute evidence for a brighter future where the therapeutic use of lactobacilli can be harnessed to improve women’s health

Management strategies for POSEIDON groups 3 and 4

In the POSEIDON classification, patients belonging to groups 3 and 4 share the same common feature of a poor ovarian reserve which independently of age renders them at high risk of a poor reproductive outcome. Overall, POSEIDON groups 1-4 constitute approximately 47% of patients attending assisted reproductive technology (ART) treatment. With the increasing delay in childbearing, POSEIDON group 4 seems to increase in numbers now in some centers constituting more than 50% of the total POSEIDON population, whereas group 3 patients constitute approximately 10%. Both POSEIDON groups 3 and 4 patients require special attention as regards pre-treatment strategy, ovarian stimulation, adjuvant treatment, and ovulation trigger strategy in order to optimize the probability of having at least one euploid blastocyst for transfer. Although more evidence is needed, recent advances seem to have increased the reproductive outcomes in the poor prognosis patient. The key to success is individualization in all steps of ART treatment. Herein, we review the recent evidence for the management of POSEIDON groups 3 and 41

Management Strategies for POSEIDON Groups 3 and 4

In the POSEIDON classification, patients belonging to groups 3 and 4 share the same common feature of a poor ovarian reserve which independently of age renders them at high risk of a poor reproductive outcome. Overall, POSEIDON groups 1-4 constitute approximately 47% of patients attending assisted reproductive technology (ART) treatment. With the increasing delay in childbearing, POSEIDON group 4 seems to increase in numbers now in some centers constituting more than 50% of the total POSEIDON population, whereas group 3 patients constitute approximately 10%. Both POSEIDON groups 3 and 4 patients require special attention as regards pre-treatment strategy, ovarian stimulation, adjuvant treatment, and ovulation trigger strategy in order to optimize the probability of having at least one euploid blastocyst for transfer. Although more evidence is needed, recent advances seem to have increased the reproductive outcomes in the poor prognosis patient. The key to success is individualization in all steps of ART treatment. Herein, we review the recent evidence for the management of POSEIDON groups 3 and 4