Hormonal profile in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients.

The major limitations associated with gonadotropin-releasing hormone agonist (GnRHa) triggering are inferior clinical outcomes in fresh embryo transfer cycles caused by luteal phase insufficiency following the GnRHa triggering. We included 153 high-risk patients in this study. In group I, the patients received gonadotropin-releasing hormone agonist (GnRHa) trigger + 1,500 IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day; in group II, the patients had a dual trigger (GnRHa + 1,500 IU hCG); and in group III (control), 10,000 IU hCG trigger was prescribed for the final oocyte maturation. The levels of LH, estradiol, and progesterone were evaluated in serum on the stimulation starting day, day 6 of stimulation, on the day of the trigger administration, OPU day, days 3 and 5 post-OPU, and day 14 post-ET, as well as in follicular fluid. Progesterone concentration was significantly lower in group I on OPU+5 compared to the hCG group (I vs. III, р = 0.0065). Progesterone levels were significantly lower in group II in serum on OPU+5 compared to groups I and III (I vs. II, р = 0.0068; II vs. III, р = 1.76 × 108). The progesterone levels were significantly higher in follicular fluid in group III compared to the study groups (I vs. III, р = 0.002; II vs. III, p = 0.009). However, no significant differences in clinical outcomes were found between the groups. Then, we divided all women into pregnant and non-pregnant groups and found that estradiol (p = 0.00009) and progesterone (p = 0.000036) on the day of the pregnancy test were significantly higher in the pregnant women group. Also, progesterone on OPU day was significantly higher in the non-pregnant group (p = 0.033). Two cases of moderate ovarian hyperstimulation syndrome (OHSS) late-onset occurred in group I (3.5%, 2/56), no case of moderate/severe OHSS late-onset in group II, and three cases of moderate late-onset in group III (5.7%, 3/53). The low-dose hCG supplementation improves the luteal phase insufficiency after GnRHa triggering, which is confirmed by the comparable pregnancy rates in fresh transfer cycles between the groups. However, low-dose hCG carries a similar risk of OHSS as the full dose of hCG in high-responder patients.

Follicular waves in ontogenesis and female fertility.

Antral follicle growth and recruitment are the basis of female reproduction. Follicular wave theory explains the recruitment, growth, and selection of antral follicles. This article is devoted to the follicular wave pattern in female reproduction throughout life. We highlight progress in understanding the rhythmic follicle changes based on clinical studies and studies on animal models. We review the follicular wave pattern before puberty, during pregnancy, and in perimenopause. Several mathematical models are known which quite accurately describe follicular wave dynamics. The follicular waves theory allows the implementation of the new approaches to ovarian stimulation. Stimulation in the luteal phase and double stimulation are used more widely nowadays for fertility preservation in cancer patients and for increasing the chances of IVF programs success in poor responder patients.

Angiogenic cytokine and interleukin 8 levels in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients.

PROBLEM: Interleukin 8 (IL-8), vascular endothelial growth factor A (VEGFA), its receptors 1 (VEGFR1) and 2 (VEGFR2) are associated with ovarian hyperstimulation syndrome (OHSS) pathophysiological mechanisms. The aim of this study was to evaluate the concentrations of these cytokines depending on the way of ovulation triggering. METHOD OF STUDY: A total of 51 high-responder patients underwent IVF program and received gonadotropin-releasing hormone agonists (GnRHa) trigger + 1500 IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day (group I), dual trigger (GnRHa + 1500 IU hCG; group II), or hCG trigger 10,000 IU (group III) for the final oocyte maturation. The concentrations of cytokines were evaluated in serum by the enzyme-linked immunosorbent assay kit. RESULT(S): VEGFR2 levels were significantly lower in groups I and II than in group III in serum on the OPU (I vs. III, p = .0456; II vs. III, p = .0122) and OPU + 5 day (I vs. III, p = .0004; II vs. III, p = .0082). VEGFA levels were lower in group I than in group III (p = .0298) on the OPU day, however, were similar in all groups on the OPU + 5 day. CONCLUSION(S): A small dose of hCG elicits similar concentrations of VEGFA to a full dose of hCG; however, GnRHa triggering reduces the concentrations of VEGFR2, which could lead to the OHSS prevention.

Cumulus cell gene expression in luteal-phase-derived oocytes after double stimulation in one menstrual cycle.

RESEARCH QUESTION: Does double stimulation (DuoStim) affect cumulus cell gene expression in luteal-phase-derived oocytes? DESIGN: This prospective observational study included 39 patients with reduced ovarian reserve. Fifteen patients (group 1) underwent IVF with a gonadotrophin-releasing hormone antagonist in the follicular phase and 24 patients (group 2) underwent DuoStim. A total of 149 cumulus cell samples were divided into two groups according to the phase of the cycle: group 1 included 55 follicular-phase-derived oocytes and group 2 included 94 luteal-phase-derived oocytes. The expression levels of the following genes were assessed using quantitative polymerase chain reaction: HAS2, VCAN, ALCAM, PTGS2, GREM1, ITPKA, TRPM7, SDC4, CALM2, SPSB2, TP53I3, PGR and PFKP. RESULTS: The expression of 10 out of 13 genes in cumulus cells was similar between DuoStim luteal-phase-derived oocytes and follicular-phase-derived oocytes. A significant increase in the mRNA levels of VCAN (15.542 ± 6.8 versus 20.353 ± 10.58; P = 0.001), SDC4 (1.016 ± 0.65 versus 1.318 ± 0.97; P = 0.013), and TP53I3 (0.185 ± 0.09 versus 0.270 ± 0.11; P = 1.19E-05) was observed in group 2. The number of oocytes collected (5.57 ± 2.3 versus 5.7 ± 2.7; P > 0.05) and the number of blastocysts were comparable between the groups (2.1 ± 2.1 versus 2.7 ± 2.2; P > 0.05). CONCLUSIONS: The DuoStim approach leads to changes in the follicular environment. It affects the expression levels of VCAN, SDC4, and TP53I3 in the cumulus cells of luteal-phase-derived oocytes. These results, however, did not correlate with oocyte maturation, embryo quality and pregnancy rate.

Should we transfer poor quality embryos?

BACKGROUND: To evaluate if it is safe and effective to transfer poor quality embryos. METHODS: It was a retrospective analysis using individual patient data with positive controls. All patients undergoing embryo transfers of poor quality embryos on day 3 or on day 5 as part of fresh In Vitro Fertilization (IVF) cycles performed between 2012 and 2016. This study assessed a total of 738 poor quality embryos from 488 IVF programs. 261 embryo transfers were performed on day 3 (402 embryos were transferred) and 227 on day 5 (336 embryos were transferred). Control group consisted of 9893 fair and good quality embryos from 5994 IVF programs. Outcome rates were compared with two-tailed Fisher exact test using fisher.test function in R software. 95% confidence intervals for proportions were calculated using the Clopper-Pearson method with binom.test function in R. The groups of patients with poor vs. good and fair quality embryos were compared by age, body mass index(BMI), number of oocytes, female and male main diagnosis, cycle type, controlled ovarian stimulation (COS) protocol, the starting day of gonadotropin administration, the starting dose of gonadotropins, the total dose of gonadotropins, the total number of days of gonadotropins administration, the starting day of gonadotropin-releasing hormone (GnRH) agonist administration, the total number of ampoules of GnRH-agonist used, day of the trigger of ovulation administration and the type of the trigger of ovulation using the Student's t-test for interval variables and with the chi-square test for nominal variables. RESULTS: No significant differences in the implantation rate, clinical pregnancy rate, miscarriage rate, live births, and the number of children born were found between the groups of poor quality embryos transferred on day 3 and day 5. Though the implantation rate was lower for the group of poor quality embryos, than for the control (13.9% vs 37.2%), statistically significant differences between the proportion of implanted embryos which resulted in clinical pregnancies and live births in both groups were not observed (72% vs 78.2 and 55.8% vs 62.0% respectively). CONCLUSION: Transfer of poor quality embryos at either day 3 or day 5 have a low potential for implantation, though those embryos which successfully implanted have the same potential for live birth as the embryos of fair and good quality. This study supports that it is safe to transfer poor quality embryos when they are the only option for fresh embryo transfer (ET).