Growth Hormone Cotreatment for Low-Prognosis Patients According to the POSEIDON Criteria

BackgroundPoor ovarian response (POR) remains one of the most challenging conditions in assisted reproduction technology. Previous studies seemed to indicate that growth hormone (GH) was a potential solution for the dilemma of POR; however, the role GH played on the low-prognosis patients diagnosed and stratified by the POSEIDON criteria remains indistinct.MethodsThis retrospective study was performed among women with POR according to the POSEIDON criteria who failed a previous in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle, and the subsequent cycle was under GH cotreatment and conducted within 12 months. These participants were stratified into four groups according to the POSEIDON criteria. The comparison was implemented between the failed cycle and the cycle treated with GH. Generalized estimating equation (GEE) multivariate regression was applied for data analysis.ResultsA total of 428 low-prognosis women were included in this study. GH supplementation improved the live birth rates (47.66%, 28.33%, 45.45%, and 24.07%; in groups 1, 2, 3, and 4, respectively) and the clinical pregnancy rates (OR 19.16, 95% CI 7.87–46.63, p < 0.001; OR 7.44, 95% CI 1.65–33.55, p = 0.009; OR 10.19, 95% CI 2.39–43.52, p = 0.002; OR 27.63, 95% CI 4.46–171.11, p < 0.001; in groups 1, 2, 3, and 4, respectively) in all four POSEIDON groups. The number of oocytes retrieved was significantly elevated in the subgroups with normal ovarian reserve (IRR 1.47, 95% CI 1.36–1.59, p < 0.001; IRR 1.31, 95% CI 1.15–1.49, p < 0.001; in groups 1 and 2, respectively). The number of day-3 good-quality embryos was significantly elevated in the subgroups with either normal ovarian reserve or aged young (IRR 2.13, 95% CI 1.78–2.56, p < 0.001; IRR 1.54, 95% CI 1.26–1.89, p < 0.001; IRR 1.47, 95% CI 1.10–1.98, p = 0.010; in groups 1, 2, and 3, respectively).ConclusionGrowth hormone cotreatment could ameliorate the pregnancy outcome for women with POR under the POSEIDON criteria who failed a previous IVF/ICSI cycle. The application of growth hormone for low-prognosis women who experienced a failed cycle might be considered and further studied.

Is there any role of interleukin-6 and high sensitive C-reactive protein in predicting IVF/ICSI success? A prospective cohort study

Objectives Studies have established a relationship between proinflammatory factors and implantation failure in IVF/ICSI cycles. Likewise, low-grade chronic inflammation is generally blamed for predisposing infertility. In the present study, we aimed to find a relationship between serum IL-6 and hs-CRP levels and IVF/ICSI cycle outcomes. Methods A total of 129 patients who consented to participate and attended the IVF unit of our department for the treatment of infertility have been enrolled in this prospective cohort study. Serum levels of high sensitive C-reactive protein and interleukin 6 have been detected at the beginning of the IVF/ICSI ovulation induction cycle. Cycle outcomes have been compared between patients with and without clinical pregnancy achievement following ART treatments. IVF/ICSI cycle outcomes of these two groups were also comparable except the number of >14 mm follicles, retrieved oocytes, metaphase II oocytes, and fertilized oocytes (2 pronuclei) which were in favor of the clinical pregnancy group. Results Mean serum hs-CRP levels were 3.08 mg/L (0.12–35.04) and 2.28 mg/L (0.09–22.52) patients with and without clinical pregnancy respectively. Mean serum IL-6 levels were 2 pg/mL (1–10.2) and 2 pg/mL (1–76.9) patients with and without clinical pregnancy respectively. Both tests were found to be statistically insignificant in predicting the success of the ART cycle in terms of implantation, clinical pregnancy, miscarriage, and live birth. Conclusions In the present study, we have not found any significant effect of hs-CRP and IL-6 levels in the IVF cycle. However, in the light of this and previous studies, large-scale research may prove the exact influence of these markers on IVF success.

Correlation of Pregnancy-Associated Plasma Protein (PAPP-A) in Serum and Follicular Fluid with Oocyte and Embryo Quality in PCOS and non-PCOS Women Undergoing ICSI Cycle

Pregnancy-Associated Plasma Protein (PAPP-A) is a zinc metalloproteinase in the insulin growth factor system (IGFs) produced by the syncytiotrophoplast region of the placenta. It plays a critical function in the cleavage of IGFBP4. In the ovary IGFs, it regulates follicular and oocyte maturation, and steroidogenesis. While in polycystic ovarian syndrome (PCOS) Hyperinsulinemia and hyperandrogenemia it causes follicular environment changes and early ovulation resulting in lower oocyte and embryo quality in patients and this will decrease the success of pregnancy in women enrolled in the ICSI cycle. The present study aimed to assess the relationship of PAPP-A levels in serum and follicular fluid in women with PCOS and non-PCOS with oocyte and embryo quality in women undergoing ICSI cycle. 45 infertile Iraqi women were enrolled. Women with PCOS had to meet at least two of the three criteria set by the Rotterdam ESHRE/ASRMS criteria, the age of the included women ranged between 20-45 years. In non-PCOS patients, PAPP-A has higher level in serum and follicular fluid but without a statistically significant difference matching with PCOS group. In addition, there was no significant correlation between PAPP-A levels in serum and follicular fluid with oocytes and embryo characteristics. However, PAPP-A levels are higher in serum and follicular fluid in women with positive pregnancy but without significant differences. PAPP-A had no correlation with oocyte and embryo quality.

Early Follicular Phase Human Chorionic Gonadotropin Addition May Improve the Outcomes of In Vitro Fertilization/Intracytoplasmic Sperm Injection in Patients With “Unpredictable” Poor Response to Gonadotropin-Releasing Hormone Antagonist Protocol

PurposeTo compare the effects of early and mid-late follicular phase administration of 150 IU of human chorionic gonadotropin (hCG) on gonadotropin-releasing hormone (GnRH) antagonist protocol in “unpredictable” poor ovarian response (POR) women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.MethodsA retrospective single-center cohort study was conducted on 67 patients with “unpredictable” POR in their first IVF/ICSI cycle receiving GnRH antagonist protocol. Patients were treated with a second IVF/ICSI cycle using the same GnRH antagonist protocol with the same starting dose of recombinant follicle-stimulating hormone (rFSH) as the first cycle; a daily dose of 150 IU of hCG was administrated on either stimulation day 1 (Group A, n = 35) or day 6 (Group B, n = 32). The number of oocytes retrieved, number of usable embryos, serum level of estradiol (E2) on day of hCG trigger, and clinical pregnant outcomes were studied.ResultsThe addition of 150 IU of hCG on either the first day or sixth day of stimulation increases the serum level of E2, luteinizing hormone (LH), and hCG on the day of hCG trigger. Only the use of 150 IU of hCG on the first stimulation day improved the number of oocytes retrieved, mature of oocytes, and usable embryos, but not the addition of hCG on stimulation day 6. Implantation rate, clinical pregnancy rate, and ongoing pregnancy rate showed an increasing trend in patients receiving 150 IU of hCG in the early phase compared with mid-late phase, even thought there was no statistically significant difference.ConclusionsOur study demonstrated that adding 150 IU of hCG in subsequent GnRH antagonist cycle in “unpredictable” poor responders is associated with the improvement of response to stimulation. Furthermore, early follicular phase addition of 150 IU of hCG significantly increased the number of oocytes retrieved and usable embryos than did the mid-late addition of the same dose.

Improving Implantation Rate in 2nd ICSI Cycle through Ovarian Stimulation with FSH and LH in GNRH Antagonist Regimen

Objective To investigate whether patients with a previous recombinant follicle stimulating hormone (rFSH)-stimulated cycle would have improved outcomes with rFSH + recombinant luteinizing hormone (rLH) stimulation in the following cycle. Methods For the present retrospective case-control study, 228 cycles performed in 114 patients undergoing intracytoplasmic sperm injection (ICSI) between 2015 and 2018 in an in vitro fertilization (IVF) center were evaluated. Controlled ovarian stimulation (COS) was achieved with rFSH (Gonal-f, Serono, Geneva, Switzerland) in the first ICSI cycle (rFSH group), and with rFSH and rLH (Pergoveris, Merck Serono S.p.A, Bari, Italy) in the second cycle (rFSH + rLH group). The ICSI outcomes were compared among the groups. Results Higher estradiol levels, oocyte yield, day-3 high-quality embryos rate and implantation rate, and a lower miscarriage rate were observed in the rFSH + rLH group compared with the rFSH group. In patients < 35 years old, the implantation rate was higher in the rFSH + rLH group compared with the rFSH group. In patients ≥ 35 years old, higher estradiol levels, oocyte yield, day-3 high-quality embryos rate, and implantation rate were observed in the rFSH + rLH group. In patients with ≤ 4 retrieved oocytes, oocyte yield, mature oocytes rate, normal cleavage speed, implantation rate, and miscarriage rate were improved in the rFSH + rLH group. In patients with ≥ 5 retrieved oocytes, higher estradiol levels, oocyte yield, and implantation rate were observed in the rFSH + rLH group. Conclusion Ovarian stimulation with luteinizing hormone (LH) supplementation results in higher implantation rates, independent of maternal age and response to COS when compared with previous cycles stimulated with rFSH only. Improvements were also observed for ICSI outcomes and miscarriage after stratification by age and retrieved oocytes.

Comparison of GnRH Agonist, hCG, and Dual Trigger for Final Oocyte Maturation in ICSI Cycle. A Case Control Study

BACKGROUND:Gonadotrophin-releasing hormone (GnRH) agonist has been proposed as an alternative drug to human chorionic Gonadotropin (hCG) for triggering. The purpose of this study to analyze the effects of three types of trigger hCG, GnRH-a or combine of them (dual) on quality of oocyte and embryoand ovarian hyperstimulation syndrome (OHSS)in the ICSI cycle. METHODS:A prospective case control study was conducted on 320 women who referred to Milad, IVF Center, Mashhad, Iran, between May 2016 and June 2019. All patients underwent antagonist protocol and were classified according to the type of trigger in three groups, 118 patients in the GnRH-agroup, 49 patients in the hCG group, and 153in dualgroup. The oocytes were retrieved after 36 hours of injection of the trigger. The outcome measures were the number ofmetaphase I,metaphase II oocyte, Germinal vesicle (GV) oocytes, high-quality embryo and rate of OHSS.RESULTS:Three groups were not significantly different in terms of the proportion of retrieved oocytes, the number of embryos, M I oocyte, M II oocyte, and the number of GV oocytes. The quality of embryos between the three groups was difference significantly (p<.05). In comparison to dual and GnRH-a group trigger, women who received hCG group had a higher number of OHSS, and the number of severe OHSS in dual trigger was higher than GnRH-a vs and hCG groups.CONCLUSIONS: GnRH agonist alone and dual trigger (hCG, GnRHagonist) can be as effective as hCG trigger. GnRH agonist is preferable in high risk patient. Therefore, it should be used according to the patient’s condition.

Calcium Ionophore (A23187) Rescues the Activation of Unfertilized Oocytes After Intracytoplasmic Sperm Injection and Chromosome Analysis of Blastocyst After Activation

Calcium is a crucial factor in regulating the biological behavior of cells. The imbalance of calcium homeostasis in cytoplasm will cause abnormal behavior of cells and the occurrence of diseases. In intracytoplasmic sperm injection (ICSI) cycle, the dysfunction of oocyte activation caused by insufficient release of Ca2+ from endoplasmic reticulum is one of the main reasons for repeated fertilization failure. Calcium ionophore (A23187) is a highly selective calcium ionophore, which can form stable complex with Ca2+ and pass through the cell membrane at will, effectively increasing intracellular Ca2+ levels. It has been reported that calcium ionophore (A23187) can activate oocytes and obtain normal embryos. However, there are few studies on unfertilized oocytes after calcium ionophore (A23187) rescue activation in ICSI cycle. The purpose of this study was to analyze the effects of calcium ionophore (A23187) rescue activation on the activation of unfertilized oocytes, embryonic development potential, embryonic development timing and chromosomal aneuploidy, and to compare and analyze the clinical data of patients with calcium ionophore (A23187) activation in clinical application. The results showed that a certain proportion of high-quality blastocysts with normal karyotype could be obtained after calcium ionophore (A23187) rescue activation of unfertilized oocytes, and it did not have a significant effect on the timing of embryo development. In clinical practice, direct activation with calcium ionophore (A23187) after ICSI was better than rescue activation the next day. In conclusions, the studies on the effectiveness and safety of calcium ionophore (A23187) rescue activation for oocytes with ICSI fertilization failure can enable some patients to obtain usable, high-quality embryos during the first ICSI cycle.