Gonadotropin-releasing Hormone Antagonist Protocol Research Articles

GnRH antagonist alters the migration of endometrial epithelial cells by reducing CKB.

Some studies have demonstrated that the implantation rate of fresh transfer cycles is lower in the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol than in the GnRH agonist (GnRH-a) protocol during in vitro fertilization (IVF). This effect may be related to endometrial receptivity. However, the mechanisms are unclear. Here, endometrial tissues obtained from the mid-secretory phase of patients treated with GnRH-a or GnRH-ant protocols and from patients on their natural cycle were assessed. Endometrial expression of B-type creatine kinase (CKB), which plays important roles in the implantation phase, was significantly reduced in the GnRH-ant group. At the same time, expression of the endometrial receptivity marker HOXA10 was considerably reduced in the GnRH-ant group. GnRH-ant exposure in endometrial epithelial cells (EECs) in vitro decreased CKB expression and ATP generation and blocked polymerization of actin. Furthermore, in vitro GnRH-ant-exposed Ishikawa cells showed enhanced F-actin depolymerization, and these effects were rescued by CKB overexpression. Similar effects were observed after CKB knockdown, and these effects were rescued by CKB overexpression. Moreover, cell migration was decreased in CKB-knockdown Ishikawa cells compared with that in control cells, and this effect was also rescued by CKB overexpression. Overall, these findings showed that GnRH-ant affected CKB expression in EECs, resulting in cytoskeletal damage and migration failure. These results provide insight into the roles and molecular mechanisms of GnRH-ant treatment in the endometrium.

Dual trigger protocol is an effective IVF strategy in both normal and high responders without compromising pregnancy outcomes

To compare pregnancy outcomes between normal versus high responders after dual trigger of final oocyte maturation with gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG) in fresh in-vitro fertilization (IVF) cycles, where ovarian stimulation was achieved by a flexible GnRH antagonist protocol.

The performance of the Elecsys® anti-Müllerian hormone assay in predicting extremes of ovarian response to corifollitropin alfa

What is the performance of anti-Müllerian hormone (AMH) as measured by the Elecsys® AMH assay in predicting ovarian response in women treated with 150 µg corifollitropin alfa (CFA)? Multicentre, prospective study conducted between December 2015 and April 2018. Women were aged 18-43 years, had regular menstrual bleeding, a body mass index of 17-35 kg/m2 and weighed 60 kg or over. previous oophorectomy, history of ovarian hyperstimulation syndrome, a previous IVF and intracytoplasmic sperm injection cycle producing over 30 follicles measuring 11 mm or wider, basal antral follicle count (AFC) over 20 or polycystic ovarian syndrome. All women were treated with 150 μg CFA followed by recombinant FSH (150-300 IU/day) in a fixed gonadotrophin releasing hormone antagonist protocol. Of the 219 patients enrolled, 22.8% had low ovarian response (three or fewer oocytes), 66.2% had normal response and 11% had high ovarian response (15 or more oocytes). The AMH and AFC presented an area under the curve of 0.883 (95% CI 0.830 to 0.936) and 0.879 (95% CI 0.826 to 0.930), respectively, for low ovarian response; and an AUC of 0.865 (95% CI 0.793 to 0.935) and 0.822 (95% CI 0.734 to 0.909) for high ovarian response. An AMH cut-off of 1.0 ng/ml provided a sensitivity of 92.0% and a specificity of 66.9% in the prediction of low ovarian response; a cut-off of 2.25 ng/ml predicted high ovarian response with a sensitivity of 54.2% and a specificity of 91.8%. The automated Elecsys® AMH assay predicts ovarian response in a CFA antagonist protocol. The best predictors of ovarian response in CFA-treated patients were AMH and AFC.

Is ovarian response associated with adverse perinatal outcomes in GnRH antagonist IVF/ICSI cycles?

Is there an association between ovarian response and perinatal outcomes? A retrospective, single-centre cohort study including all women undergoing their first ovarian stimulation cycle in a gonadotrophin releasing hormone antagonist protocol, with a fresh embryo transfer that resulted in a singleton live birth from January 2009 to December 2015. Patients were categorized into four groups according to the number of oocytes retrieved: one to three (category 1), four to nine (category 2), 10-15 (category 3), or over 15 oocytes (category 4). The overall number of patients analysed was 964. No relevant statistical difference was found among neonatal outcomes across the four ovarian response categories. Neonatal weight (in grams) was comparable between all groups (3222 ± 607 versus 3254 ± 537 versus 3235 ± 575 versus 3200 ± 622; P = 0.85, in categories 1, 2, 3 and 4, respectively). No statistically significant differences were found among the ovarian response categories for birth weight z-scores (taking into account neonatal sex and delivery term). The incidence of pre-term birth and low birth weight was comparable across the different ovarian response groups (P = 0.127 and P = 0.19, respectively). Finally, the occurrence of adverse obstetric outcomes did not differ among the ovarian response categories. Multivariate regression analysis revealed that the number of oocytes was not associated with neonatal birth weight. No association was found between ovarian response and adverse perinatal outcomes in antagonist IVF and intracytoplasmic sperm injection cycles. Future, larger scale and prospectively designed investigations are needed to validate these results.

Comparison of Highly Purified HMG versus Recombinant FSH with Antagonist Protocol in Poor Responder Patients

Background:Luteinizing hormone (LH) supplementation may have beneficial effect on the maturity and fertilizability of oocytes in poor ovarian reserve (POR) and may influence the progesterone level, thus increasing the pregnancy rate. However, previous studies on the effect of LH activity supplementation on poor responders have shown conflicting results. This study aimed to compare the clinical effectiveness of two different forms of gonadotropin (highly purified human menopausal gonadotropin (HP-HMG) vs. recombinant human follicle-stimulating hormone (r-hFSH)-only) in Indonesian population.Methods: Women diagnosed with poor ovarian response who received gonadotropin-releasing hormone (GnRH) antagonist protocol with either HP-HMG or r-hFSH-only were investigated. Women who underwent freeze all cycles, mini stimulation, and natural stimulation were excluded. Multiple logistic regression was performed to assess the effect of follicle-stimulating hormone (FSH) + human chorionic gonadotropin (HCG)-driven LH activity combination in HP-HMG to pregnancy event adjusting for progesterone level, demographic variables, and clinical characteristic variables.Results: A total of 101 subjects in the HP-HMG treatment group and 89 subjects in r-hFSH-only treatment group were involved in the study. There was no significant difference of clinical pregnancy rate between HP-HMG group and r-hFSH-only group (adjusted OR: 0.94, 95% CI: 0.39–2.25; p-value: 0.890).Conclusion: Compared to r-hFSH-only group, combination of FSH + HCG-driven LH activity in HP-HMG group had similar effectiveness in poor responders undergoing in vitro fertilization (IVF) using the antagonist protocol.

Dose-Dependent Chlormadinone Acetate Can Suppress Premature LH Surge in Parallel with LH Value Reduction

Background: Progestin-primed ovarian stimulation (PPOS) protocol is reported as an alternative method of premature luteinizing hormone (LH) surge suppression. How much dosage of chlormadinone acetate (CMA), a synthetic progestin, is appropriate treatment for this phenomenon? Methods: Retrospective case control study was performed at private assisted reproductive technology (ART) clinic in Japan. Collected data was 231 cycles in patients who underwent either PPOS protocol using 12, 6, 4, or 2 mg of CMA, groups 6C, 3C, 2C, and 1C, respectively (total, 113 cycles), or gonadotropin-releasing hormone (GnRH) antagonist protocol, groups 6A, 3A, 2A, and 1A, respectively (total, 118 cycles). In the CMA group, CMA and human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) were administered simultaneously beginning on menstrual cycle day 3. Serum P, E2, and LH were determined on the day of human chorionic gonadotropin (hCG) administration. Occurrence of premature LH surge was compared between two groups. Pregnancy outcomes were also calculated. Results: Premature LH surge was completely suppressed in CMA groups 6C, 3C, and 2C. On the other hand, this phenomenon was detected in antagonist method groups (5.9%, 7/118). But spontaneous ovulation was not observed in any group, and clinical outcomes are equal to those of GnRH antagonist treatment. Conclusions: Controlled ovarian stimulation (COS) using CMA can be an appropriate alternative progestin for PPOS protocol. Since CMA is an oral medication, this method can be easy to conduct and cost-effective compared with the antagonist method. From our observation, we suggest 4 mg/day of CMA can control the egg retrieval cycle without LH surge occurrence as in other PPOS methods.

Extended Letrozole Regimen Co-treatment With Gonadotropin Releasing Hormone Antagonist Protocol Versus Gonadotropin Releasing Hormone Antagonist Protocol in Poor Responders Undergoing IVF-ET

Extended Letrozole Regimen Co-treatment With Gonadotropin Releasing Hormone Antagonist Protocol Versus Gonadotropin Releasing Hormone Antagonist Protocol in Poor Responders Undergoing IVF-ET

Comparison of antral follicle count and serum anti Müllerian hormone level for determination of gonadotropin dosing in in-vitro fertilization: randomized trial.

To compare the proportion of women achieving a desired ovarian response following ovarian stimulation when gonadotropin dosing was determined based on antral follicle count (AFC) vs serum anti-Müllerian hormone (AMH) level, in women undergoing in-vitro fertilization (IVF) using the gonadotropin-releasing hormone (GnRH) antagonist protocol. This was a randomized double-blind trial carried out in a university-affiliated assisted reproduction unit. A total of 200 women undergoing their first IVF cycle using the GnRH-antagonist protocol between April 2016 and February 2018 were randomized to determination of gonadotropin dosing based on either AFC or serum AMH level measured in the pretreatment cycle 1 month before the IVF cycle. Patients underwent IVF as per our center's standard protocol. The proportion of subjects achieving a desired ovarian response, defined as retrieval of six to 14 oocytes, was compared between the two study arms. Subgroup analysis of patients with baseline AFC > 5 and those with baseline AFC ≤ 5 was performed. Concordance in AFC and AMH categorization between the pretreatment cycle and the ovarian-stimulation cycle was assessed using Cohen's kappa (κ). There was no significant difference in the proportion of patients achieving a desired ovarian response between the AFC (54%) and AMH (49%) groups (P = 0.479). The median number of oocytes retrieved was nine vs seven (P = 0.070), and the median follicular output rate was 0.54 vs 0.55 (P = 0.764) in the AFC and AMH groups, respectively. Similar findings were observed on subgroup analysis of subjects with AFC ≤ 5 and AFC > 5 at the start of ovarian stimulation (P > 0.05 for all comparisons). There was moderate concordance between AFC and AMH measured in the pretreatment cycle and the stimulation cycle (κ = 0.478 and 0.587, respectively). The proportion of women achieving a desired ovarian response following ovarian stimulation using the GnRH-antagonist protocol is similar when the gonadotropin-dosing algorithm used is based on AFC or serum AMH level. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Effect of oral Utrogestan in comparison with Cetrotide on preventing luteinizing hormone surge in IVF cycles: A randomized controlled trial.

BackgroundOral progesterone is recommended as an alternative to gonadotropin-releasing hormone (GnRH) agonists and antagonists to prevent luteinizing hormone (LH) surge in assisted reproductive technology (ART) cycles. However, there are little data regarding its use.ObjectiveWe aimed to compare the effect of oral Utrogestan and Cetrotide (a GnRH antagonist) on preventing LH surge in ART cycles.Materials and MethodsIn this randomized clinical trial, 100 infertile women undergoing ART who received recombinant follicle-stimulating hormone (FSH) at 150-225 IU/day were randomly assigned to receive either Utrogestan 100 mg twice a day (case group) or GnRH antagonist protocol (control group) from cycle day 3 until the trigger day. Triggering was performed with 10,000 IU hCG) when there were at least three mature follicles. Viable embryos were cryopreserved for transfer in the next cycle for both groups. The number of oocytes retrieved and transferred embryos were compared between groups.ResultsThe case group had significantly higher progesterone levels on triggering day, more follicles of 14 mm with higher maturity, and more oocytes retrieved with a higher rate of embryos transferred. A small increase in the pregnancy rate was observed in the case group, with no significant between-group differences. The most important result was the lack of premature LH surge in either group upon serum LH assessment on the triggering day.ConclusionUtrogestan is an alternative treatment that could reduce the LH surge rate and increase the ART outcomes including the number of oocytes retrieved and transferred embryos compared with GnRH agonists and antagonists

Transvaginal ovarian drilling followed by controlled ovarian stimulation from the next day improves ovarian response for the poor responders with polycystic ovary syndrome during IVF treatment: a pilot study

BackgroundPoor response patients with PCOS who are not susceptible to gonadotropin stimulation are more likely to have canceled cycles or poor clinical outcomes during IVF treatment. However, some limitations exist in the present therapies. In this study, we evaluated the effects of using the transvaginal ovarian drilling (TVOD) followed by controlled ovarian stimulation (COS) from the second day of these poor responders.MethodsDuring IVF, 7 poor responders with PCOS and 28 PCOS patients (14 normal and 14 high responders) were recruited. All patients received COS with the gonadotropin-releasing hormone antagonist protocol. For the poor responders, after undergoing 10 to 14 days of ovulation induction with no response, the TVOD was applied and then ovarian stimulation was performed from the next day at the same gonadotropin dose. Serum samples during COS and follicular fluid samples from the dominant follicles on the oocyte pick-up (OPU) day in all three groups were collected. Besides, follicular fluid from small follicles (diameter < 1 cm) in the normal and high responders on the OPU day and those in the poor responders on the TVOD day were gathered. Hormonal levels were examined in all samples using immunometric assays.ResultsAll the poor responders restored ovary response after receiving TVOD. There was no significant difference in the stimulation duration, total gonadotrophin dose used and the clinical outcomes among the three groups. The body mass index, serum and follicular levels of anti-Müllerian hormone (AMH) and testosterone in poor responders were higher than those in the other two groups, and the application of TVOD significantly decreased the levels of AMH and testosterone in both serum and follicular fluid.ConclusionsTVOD followed by ovulation induction from the next day is effective and convenient for poor responders with PCOS. The decline of AMH and testosterone resulted from TVOD may be the main reason resulting in the recovery of ovary sensitivity to gonadotropins. The small sample size is the primary limitation of this study, future studies using a large population cohort and monitoring the long-term outcomes of this strategy will be required.Trial registrationChiCTR1900023612. Registered 04 June 2019-Retrospectively registered.

Effect of double cleavage stage versus sequential cleavage and blastocyst stage embryo transfer on clinical pregnancy rates

Objective: To compare clinical pregnancy rates following sequential day-3 and day-5 embryo transfer with double or sequential cleavage-stage transfers.Methods: This study enrolled 242 patients undergoing gonadotropin-releasing hormone antagonist protocol and fresh embryo transfer. Basal follicle stimulating hormone, luteinizing hormone, serum estradiol and anti-Müllerian hormone levels and controlled ovarian stimulation outcomes were noted. Of 242 women, 135 underwent double embryo transfer on day 2 or day 3 (the double group), 54 women underwent sequential embryo transfer on day 2 and day 3 (the D2/D3 group), and 53 underwent sequential embryo transfer on day 3 and day 5 (the D3/D5 group). Clinical pregnancy rates were compared among the groups.Results: Female age, body mass index, basal follicle stimulating hormone, luteinizing hormone and estradiol levels were similar among the groups (P>0.05). The D3/D5 group had a significantly higher number of metaphase II oocytes, fertilized oocytes and good quality embryos on day 3 compared with the double group and the D2/D3 group (P < 0.001). Clinical pregnancy rates in the double, D2/D3 and D3/D5 groups were 26.6% (36/135), 16.6% (9/54) and 37.7% (20/53), respectively. There was no significant difference in clinical pregnancy rates between the double group and the D2/D3 group (P =0.204) or the D3/D5 group (P =0.188). The D3/D5 group had significantly higher clinical pregnancy rates compared with the D2/D3 group (P =0.025).Conclusions: Sequential cleavage-stage transfer (D2/D3) or cleavage stage and blastocyst transfer (D3/D5) does not improve clinical pregnancy rates compared with double cleavage-stage embryo transfer. Although sequential transfer seems to be an effective option in certain patient populations, routine application of this technique might not be a suitable approach in an unselected population to improve assisted reproductive technology outcomes.

Gonadotropin versus Follicle-Stimulating Hormone for Ovarian Response in Patients Undergoing in vitro Fertilization: A Retrospective Cohort Comparison

Poor ovarian responders generally refer to patients who respond poorly to ovarian stimulation for assisted reproductive techniques (ART) such as in-vitro fertilization (IVF) and hence experience low live birth rate. Various controlled ovarian stimulation (COS) protocols have been developed during the past 3 decades for IVF/ICSI to improve oocyte quality and ultimately live birth rate, to increase ovarian response in POR patients, and to reduce the risk of ovarian hyperstimulation syndrome. Both highly puri?ed human menopausal gonadotropin (hp-hMG) and recombinant follicle-stimulating hormone (rFSH) have been widely used for COS during IVF/ICSI. Their in?uence on treatment outcome in women undergoing IVF/ICSI hasbeen actively debated. To compare highly purified human menopausal gonadotropin (hp-hMG) and recombinant follicle-stimulating hormone (rFSH) in patients with poor ovarian response undergoing in vitro fertilization/intracytoplasmic sperm injection with a gonadotropin-releasing hormone antagonist protocol. This retrospective cohort study included 60 patients with poor ovarian response (30 received hp-hMG and 30 received rFSH) undergoing in vitro fertilization/intracytoplasmic sperm injection with a gonadotropin-releasing hormone antagonist protocol. Pregnancy-related outcomes, ovarian response, oocyte, and embryo parameters were compared between the 2 groups. Additionally, serum insulin-like growth factor-1 and insulin-like growth factor binding protein-1 levels on the day of oocyte retrieval were compared between the 2 groups. The 2 treatments resulted in comparable numbers of oocytes retrieved and embryos, comparable oocyte retrieval rate, mature oocyte rate, and fertilization rate, and also comparable clinical pregnancy rates, implantation rates, and miscarriage rate. However, hp-hMG led to statistically insignificant higher viable embryo rate (54.0% vs 44.8%; P = 0.174) and live birth rate per pregnancy (16.7% vs 10%) versus rFSH. Finally, statistically significantly higher serum insulin-like growth factor-1 level (178.53 [13.70] ng/mL vs 164.93 [12.17] ng/mL; P = 0.01) and statistically insignificantly lower serum insulin-like growth factor binding protein-1 level (19.53 [3.56] ng/mL vs the lower insulin-like growth factor binding protein-1 level SD is (2.76 [20.83] ng/mL; P > 0.05) on the day of oocyte retrieval were associated with hp-hMG versus rFSH. hp-HMG and rFSH did not lead to significantly different treatment outcomes in patients with poor ovarian response undergoing in vitro fertilization/intracytoplasmic sperm injection with a gonadotropin-releasing hormone antagonist protocol, although significantly higher serum insulin-like growth factor-1 level and insignificantly lower serum insulin-like growth factor binding protein-1 level on the day of oocyte retrieval associated with hp-HMG might suggest a beneficial endocrine environment. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Influence of stage and grade of breast cancer on fertility preservation outcome in reproductive-aged women.

Does breast cancer spread and aggressiveness affect fertility-preservation results? Retrospective cohort study of women with breast cancer undergoing fertility-preservation treatment. age 18-38 years and use of gonadotrophin releasing hormone antagonist protocol; exclusion criteria: recurrent cancer, previous oncological treatment, previous ovarian surgery and known ovarian pathology. Stimulation cycle outcomes of women with low-stage breast cancer were compared with those with high-stage disease. Patients with low-grade (G1-2) were compared with those with high-grade (G3) malignancies. total number of mature oocytes; secondary outcomes: oestradiol level and number of follicles wider than 14 mm on the day of trigger, number of retrieved oocytes and cryopreserved embryos. The final analysis included 155 patients. Patients with high-grade tumours (n = 80; age 32 years [28-35]) had significantly lower number of mature oocytes compared with patients with low-grade cancer (n = 75; age 32 years [28-35]; seven mature oocytes [4-10] versus 13 mature oocytes [7-17]; P = 0.0002). The number of cryopreserved embryos was also lower in the high-grade group (three [2-5] versus five [3-9]; P = 0.02). Stage-based analysis revealed a similar number of mature oocytes in high-stage (n = 73; age 32 years [28-35]) compared with low-stage group (n = 82; age 33 years [28-35]; eight mature oocytes [4-13] versus nine mature oocytes [7-15]; P = 0.06). High-grade breast cancer has a negative effect on total number of mature oocytes and cryopreserved embryos.

Progestin vs. Gonadotropin-Releasing Hormone Antagonist for the Prevention of Premature Luteinizing Hormone Surges in Poor Responders Undergoing in vitro Fertilization Treatment: A Randomized Controlled Trial.

Objective: Progestin was recently used as an alternative of gonadotropin-releasing hormone (GnRH) analog for preventing premature luteinizing hormone (LH) surge with the aid of vitrification techniques, however, limited data were available about the potential of progestin in poor responders undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. We performed a randomized parallel controlled trial to investigate the difference of progestin and GnRH antagonist in poor responders.Methods: A total of 340 poor responders who met with Bologna criteria were randomly allocated into the progestin-primed ovarian stimulation (PPOS) group and GnRH antagonist group. Fresh embryo transfer was preferred in the GnRH antagonist group and freeze-all was performed in the PPOS group. The primary outcome was the incidence of premature LH surge, secondary outcomes were the number of retrieved oocytes, the number of viable embryos and the pregnancy outcomes.Results: The results showed that the incidence of premature LH surge in PPOS group was lower than that in antagonist group (0 vs. 5.88%, P < 0.05). In PPOS group, the average numbers of oocytes and viable embryos were comparable to those in GnRH antagonist group (3.7 ± 2.6 vs. 3.4 ± 2.4; 1.6 ± 1.7 vs. 1.4 ± 1.3, P > 0.05), the live birth rate was similar between the two groups (21.8 vs. 18.2%, RR 1.25 (95% confidence interval 0.73, 2.13), P > 0.05).Conclusions: The study demonstrated that PPOS had a more robust control for preventing premature LH rise than GnRH antagonist in poor responders, but PPOS in combination with freeze-all did not significantly increase the probability of pregnancy than GnRH antagonist protocol for poor responders.

Dehydroepiandrosterone Supplementation Improves the Outcomes of in vitro Fertilization Cycles in Older Patients With Diminished Ovarian Reserve.

Background: Dehydroepiandrosterone (DHEA) supplementation has been reported to have beneficial effects on the in vitro fertilization (IVF) outcomes of patients with poor ovarian response or diminished ovarian reserve. The Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) stratification is a set of newly established criteria for low prognosis patients. The aim of this study was to examine the potential effects of DHEA supplementation on the IVF outcomes of patients who fulfill the POSEIDON group 4 criteria.Methods: This retrospective cohort study investigated 297 cycles that fulfilled the POSEIDON group 4 criteria and underwent IVF treatment using the gonadotropin-releasing hormone antagonist protocol. The study group contained 159 cycles that received DHEA (30 mg three times per day) daily for 12 weeks before their IVF cycles. The control group included 138 cycles that underwent IVF cycles but did not receive DHEA. The baseline characteristics and cycle parameters as well as the IVF outcomes of both groups were compared.Results: In terms of baseline characteristics, more previous IVF attempts and lower AMH levels were found in the study group than in the control group. Regarding IVF outcomes, patients in the study group had significantly higher follicular oocyte index and higher numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality day 3 embryos than those in the control group. Besides, a higher cumulative pregnancy rate and lower cancellation rate were observed in the study group than in the control group although clinical pregnancy rate, live birth rate, and cumulative live birth rate did not differ between the two groups. Whether patients are aged ≤ 40 years or aged > 40, higher numbers of oocytes and embryos were observed in the study group than in the control group. In patients aged > 40, cumulative pregnancy rate was significantly higher in the study group than in the control group.Conclusions: Our data suggest that DHEA supplementation might increase both oocyte and embryo yields, as well as cumulative pregnancy rates, in patients fulfilling the POSEIDON group 4 criteria.

Gonadotropin-releasing hormone agonist flare-up versus Gonadotropin-releasing hormone antagonist protocols in poor responders undergoing Intra Cytoplasmic Sperm Injection ICSI.

Abstract Poor ovarian response (POR) is a multifactorial problem with less ovarian reserve and its incidence varies between 9% and 24%, therefore, early identification is It is better to reduce the risk of cycle cancellation as well as side effects. Purpose: To compare the use of Gonadotropin-releasing hormone GnRH flare-up versus GnRH antagonist protocol, in poor responders preparing for Intra Cytoplasmic Sperm Injection ICSI, as regards embryo quality, cycle parameters and clinical outcomes. Patients and methods: RCT included one hundred and six qualified poor responders performing ICSI were divided into 2 groups each containing 53 patients. Group 1 received GnRH flare-up protocol and group 2 received GnRH antagonist protocol. Data were collected for both groups. Results: No significant difference was found between both groups as regards patient age (p value 0.4), body mass index (p value 0.5), day 3 FSH level (p value 0.06), infertility cause, number of oocytes and MII oocytes and number of embryos transferred. Significant difference was found in the number of gonadotropin ampoules with less ampules in the flare-up group, 64 versus 76 ampules, peak estradiol level, which was higher in the flare-up group, 1192 versus 798 and the quality of embryos in favor of GnRH flare-up group (P-value= 0.017, 0.009 and 0.044) respectively. No significant difference was found in pregnancy and miscarriage rates (p value 0.90 and 0.87 respectively). Conclusion: Flare-up protocol is more effective than GnRH antagonist protocol as regards the improved embryo quality, with more top-quality embryos in the flare-up protocol group.

Cumulative Live Birth Rates in Low Prognosis Patients According to the POSEIDON Criteria: An Analysis of 26,697 Cycles of in vitro Fertilization/Intracytoplasmic Sperm Injection.

Objective: The POSEIDON criteria are used to stratify patients with low prognosis after assisted reproductive technology (ART) treatment. Since its introduction, there has been no large study about the prognosis of the POSEIDON population. We used the POSEIDON criteria in Chinese women who underwent repeated ART treatment and analyzed the association between POSEIDON criteria and the cumulative live-birth rate (CLBR).Methods: This was a retrospective cohort study of 62,749 women (97,388 cycles) who underwent ART treatment at the Reproductive and Genetic Hospital of CITIC-XIANGYA between January 2014 and June 2017. Among them, 19,781 (31.52%) women fulfilled the POSEIDON criteria, including 26,697 cycles. The optimal and conservative CLBRs within a complete IVF/ICSI treatment cycle were calculated, as well as the CLBRs following repeated ovarian stimulation cycles.Results: In POSEIDON groups 1, 2, 3, and 4, the optimal and conservative CLBRs of three complete consecutive in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were 83.87 and 66.06%, 53.67 and 37.72%, 44.24 and 27.98%, and 14.20 and 9.68%, respectively. The POSEIDON stratification [group 2: odds ratio (OR) = 2.319, 95% confidence interval (CI): 2.131–2.525, P < 0.001; group 3: OR = 1.356, 95% CI: 1.005–1.828, P = 0.046; group 4: OR = 3.525, 95% CI: 2.774–4.479, P < 0.001; all vs. group 1] and ovarian stimulation protocol [gonadotropin-releasing hormone (GnRH) antagonist protocol: OR = 1.856, 95% CI: 1.640–2.100, P < 0.001; other protocols: OR = 1.651, 95% CI: 1.155–2.361, P = 0.006; both vs. long GnRH agonist protocol] were associated with live birth in the first stimulation cycle. For the second stimulation cycle, the POSEIDON stratification (except POSEIDON group 3) and ovarian stimulation protocol were associated with live birth. A change in ovarian stimulation protocol was not associated with an improvement in the live birth rate.Conclusions: More than 30% of women who undergo IVF/ICSI treatment may be classified as low prognosis. Different reproductive outcomes were observed among the four POSEIDON groups. The most optimal outcomes after three successive cycles of IVF/ICSI treatment were observed in groups 1, 2, and 3.

Myoinositol supplementation on intracytoplasmic sperm injection outcome in Japanese infertile polycystic ovarian syndrome women with non-obese less-androgenic phenotype: a prospective controlled observational study

Purpose of Investigation: The objective of this prospective controlled observational study was to evaluate the effect of myoinositol supplementation on intracytoplasmic sperm injection (ICSI) outcome in Japanese infertile polycystic ovarian syndrome (PCOS) women with non-obese less-androgenic phenotype, which is common in East Asia. Materials and Methods: The ICSI outcome in the first treatment cycle under a flexible gonadotropin-releasing hormone antagonist protocol was compared between 25 PCOS women taking 4 g/day myoinositol + 400 μg/day folic acid (Myo/FA group) and 25 PCOS women taking 400 μg/day FA alone (FA Group). Results: The total dosage of human menopausal gonadtropin was significantly lower in the Myo/FA group than in the FA group (p = 0.034). The number (p = 0.000029) and rate (relative risk 1.47, 95% confidence interval 1.43-1.50, p &lt; 0.0001) of metaphase II oocytes and the number of fertilized oocytes (p = 0.0074) was significantly higher in the Myo/FA group than in the FA group. Conclusion: Myoinositol supplementation is a safe and effective treatment modality to increase the mature and fertilized oocytes, along with a reduction in the gonadotropin dose in ICSI cycles in Japanese infertile PCOS women with non-obese less-androgenic phenotype.

Comparison of a novel flexible progestin primed ovarian stimulation protocol and the flexible gonadotropin-releasing hormone antagonist protocol for assisted reproductive technology

To determine whether a flexible progestin primed ovarian stimulation (fPPOS) protocol is effective for preventing premature ovulation. Retrospective cohort study. Private assisted reproduction center. Eighty-seven oocyte donors and 191 recipients of fresh oocytes. Each donor was stimulated with a flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in one cycle and with the new fPPOS protocol in the other, within a period of 6months. FSH was started on cycle day 2-3, and 0.25mg/day GnRH antagonist or 10mg/day medroxyprogesterone acetate (MPA) was started on stimulation day 7 or when the leading follicle reached 14mm, whichever came first. Duration of stimulation, gonadotropin consumption, duration of GnRH antagonist or MPA administration, number of metaphase II oocytes, and pregnancy rates in fresh oocyte recipients. Duration of stimulation was 11 (10-11) days in both groups. Total gonadotropin consumption was similar. Pituitary suppression was started on day 7 and lasted for 5days in each group. There were no premature ovulations in any group. The fPPOS yielded a significantly higher number of cumulus oocyte complexes than GnRH antagonist cycles (33 [21-39] vs. 26 [18-36], respectively). Likewise, the fPPOS generated significantly more metaphase II oocytes than GnRH antagonist cycles (24 [17-34] vs. 21 [15-28], respectively). Recipients of fresh oocytes from fPPOS and GnRH antagonist cycles had similar cleavage, blastulation, implantation, and live birth/ongoing pregnancy rates (50% vs. 48.6%). FPPOS with MPA seems to be an effective choice for preventing premature ovulation in women undergoing ovarian stimulation without compromising oocyte quality.

A multicenter, randomized, phase III study comparing the efficacy and safety of follitropin alpha biosimilar and the original follitropin alpha

ObjectiveThe aim of the present study was to investigate the therapeutic equivalence between the follitropin alpha biosimilar and the reference medication in women undergoing assisted reproductive technologies (ART). Study designThis multicenter, randomized (1:1), embryologist-blinded, parallel-group, comparative phase III study involved 110 women aged 20–35 years old with tubal and/or male factors of infertility. All of the subjects underwent controlled ovarian hyperstimulation (COH) using a gonadotropin-releasing hormone antagonist (GnRH-ant) protocol. Over the 5-day fixed-dose regimen, the women received 150 IU/day of follitropin alpha biosimilar (n = 55) or original follitropin alpha (n = 55), followed by dose adaptation. The primary endpoint for assessing the therapeutic equivalence was the number of retrieved oocytes using a pre-determined clinical equivalence margin of ± 3.4 oocytes. ResultsSimilar numbers of oocytes were retrieved in both groups: 12.16 ± 7.28 in the follitropin alpha biosimilar group and 11.62 ± 6.29 in the original follitropin alpha group, with mean difference of 0.546 ± 1.297 oocytes (95% confidence interval [CI]: -2.026, 3.116), p = 0.002 (intention-to-treat [ITT] population). Additionally, no statistically significant differences were found for secondary endpoints: the onset of biochemical (34.7% and 36.7%, p = 0.883), clinical pregnancy (26.5% and 32.7%, p = 0.507), delivery (26.5% and 24.5%, p = 0.817) and take-home baby rate (28.6% and 26.5%, p = 0.816) for the follitropin biosimilar and original follitropin groups (per-protocol [PP] population). Ovarian hyperstimulation syndrome was observed in subjects with a positive pregnancy test in 0% and 3.64% of cases and after triggering ovulation in 7.27% and 3.64% for the follitropin biosimilar and original follitropin groups, respectively. ConclusionsThis study demonstrated similar therapeutic equivalence and safety profiles between the follitropin alpha biosimilar and the reference follitropin in women who underwent COH in GnRH-ant cycles. Trial registration number1. Name of the registry: ClinicalTrials.gov. Trial registration number: NCT03088137. Date of registration: 02.03.2017, retrospectively registered. Trial conducted between 08.02.2017 and 17.08.2018, the date of enrollment of the first participant – 08.02.2017. 2. Name of the registry: Russian Ministry of Health, grls.rosminzdrav.ru. Trial registration number: RCT 754. Date of registration: 26.10.2016, prospectively registered.