The Role of hCG Triggering Progesterone Levels: A Real-World Retrospective Cohort Study of More Than 8000 IVF/ICSI Cycles.

Objective: To assess the association between serum ovulation trigger progesterone (P) levels and the outcome of in vitro fertilization cycles. Design Setting: Real world single-center retrospective cohort study. Patient Intervention(s): All fresh cleavage and blastocyst-stage embryo transfers (ETs) performed from January 2012 to December 2016. Main outcome Measure(s): The impact of premature high serum P levels cycles in terms of clinical pregnancy rates (CPRs) and live birth rates (LBRs). Results: 8,034 ETs were performed: 7,597 cleavage-stage transfers and 437 blastocyst transfers. Serum P levels demonstrated to be inversely related to CPR (OR 0.72, p < 0.001) and LBR (OR 0.73, p < 0.001). The progressive decrease of LBR and CPR started when P levels were >1 ng/ml in a good prognosis cleavage ET subgroup, whereas in patients with worse prognosis only for P ≥ 1.75 ng/ml. In the blastocyst ET subgroup, the negative effect of P elevation was reported only if P was >1.75 ng/ml. CPR (OR 0.71 (0.62-0.80), p < 0.001) and LBR (OR 0.73 (0.63-0.84), p < 0.001) in thawed cycles resulted statistically significantly higher than in fresh cycles in the cleavage-stage subgroup. In the blastocyst group, no significant difference resulted between thawed and fresh cycles, independently of P levels [CPR OR 0. 37 (0.49-1.09), p = 0.123; LBR OR 0.71 (0.46-1.10), p = 0.126]. Conclusion: High P levels decrease CPR as well as LBR in both cleavage and blastocyst ET. In the cleavage group, for P levels below 1.75 ng/ml, our data suggest the possibility to wait until day 5 for ET, and if P level is ≥1.75 ng/ml, it should be considered to freeze all embryos and postpone the ET. Clinical Trial Registration: ClinicalTrials.gov, ID: NCT04253470.

Seven Years of Vitrified Blastocyst Transfers: Comparison of 3 Preparation Protocols at a Single ART Center.

Introduction: Frozen-thawed embryo transfers (FET) have become a standard practice to increase cumulative pregnancy rates, however, the choice of the best preparation protocol remains a matter of debate. Design: Retrospective analysis of clinical pregnancy (CPR) and live birth rate (LBR) of FET in natural cycles (NC-FET), modified natural cycles with hCG-triggered ovulation (mNC-FET), and hormonal artificial replacement (AR-FET). Materials and Methods: For natural cycles, patients were monitored by ultrasound to evaluate the dominant follicle and by urinary LH kits (NC-FET). When the endometrial thickness reached at least 7 mm and the dominant follicle 16-20 mm, hCG was administered in absence of urinary LH surge (mNC-FET). Embryo thawing and transfer was planned 7 days after LH surge or hCG administration. For the AR-FET, oral estradiol valerate was administered from day 2 of menstrual cycle until endometrial thickness reached at least 7 mm and transfer was planned after 5 days of vaginal progesterone start. Only single vitrified blastocyst transfers were included. Results: In total 2,895 transfers were performed of which 561 (19.4%) carried out with NC-FET, 1,749 (60.4%) with mNC-FET and 585 (20.2%) with AR-FET. CPRs were 32.62, 43.05, and 37.26%, respectively. LBR were 24.06, 33.56, and 25.81%, respectively. A statistically significant (p < 0.001) higher LBR for mNC-FET vs. NC-FET (OR 0.49-0.78) and AR-FET (OR 0.47-0.74) was observed. A higher ectopic pregnancy rate (p = 0.002) was observed in NC-FET (3.28%) than in AR-FET (1.83%) and mNC-FET (0.40%). A higher abortion rate (p = 0.031) in pregnancies <12 weeks was observed in AR-FET (27.52%) than in NC-FET (19.67%) and in mNC-FET (19.39%). At Post hoc analysis only female age (OR 0.91-0.95), antimullerian hormone (AMH) (OR 1.01-1.07) and mNC-FET (OR 1.39-1.98) were statically significant prognostic factors for LBRs. Conclusions: These results demonstrate a superior CPR and LBR following FET in hCG-triggered ovulation cycles compared to NC and AR-FET, a higher ectopic pregnancy rate in NC-FET and a higher abortion rate in pregnancies <12 weeks in AR-FET. However, these data need to be confirmed in randomized and prospective studies before definitive conclusions can be drawn. Clinicaltrials.gov ID: NCT03581422.

An Observational Retrospective Cohort Trial on 4,828 IVF Cycles Evaluating Different Low Prognosis Patients Following the POSEIDON Criteria.

Objective: To study the actual controlled ovarian stimulation (COS) management in women with suboptimal response, comparing clinical outcomes to the gonadotropins consume, considering potential role of luteinizing hormone (LH) addition to follicle-stimulating hormone (FSH). Design: Monocentric, observational, retrospective, real-world, clinical trial on fresh intra-cytoplasmic sperm injection (ICSI) cycles retrieving from 1 to 9 oocytes, performed at Humanitas Fertility Center from January 1st, 2012 to December 31st, 2015. Methods: COS protocols provided gonadotropin releasing-hormone (GnRH) agonist long, flare-up, short and antagonist. Both recombinant and urinary FSH were used for COS and LH was added according to the clinical practice. ICSI outcomes considered were: gonadotropins dosages; total, mature, injected and frozen oocytes; cumulative, transferred and frozen embryos; implantation rate; pregnancy, delivery and miscarriage rates. Outcomes were compared according to the gonadotropin regimen used during COS. Results: Our cohort showed 20.8% of low responders, defined as 1-3 oocytes retrieved and 79.2% of "suboptimal" responders, defined as 4-9 oocytes retrieved. According to recent POSEIDON stratification, cycles were divided in group 1 (6.9%), 2 (19.8%), 3 (11.7%), and 4 (61.5%). The cohort was divided in 3 groups, according to the gonadotropin's regimen. Women treated with FSH plus LH showed worst prognostic factors, in terms of age, basal FSH, AMH, and AFC. This difference was evident in suboptimal responders, whereas only AMH and AFC were different among treatment groups in low responders. Although a different result, in terms of oocytes and embryos detected, major ICSI outcomes (i.e., pregnancy and delivery rates) were similar among groups of COS treatment. Outcomes were significantly different among Poseidon groups. Implantation, pregnancy and delivery rates were significantly higher in Poseidon group 1 and progressively declined in other POSEIDON groups, reaching the worst percentage in group 4. Conclusions: In clinical practice, women with worst prognosis factors are generally treated with a combination of LH and FSH. Despite low prognosis women showed a reduced number of oocytes retrieved, the final ICSI outcome, in terms of pregnancy, is similarly among treatment group. This result suggests that the LH addition to FSH during COS could improve the quality of oocytes retrieved, balancing those differences that are evident at baseline. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03290911.