hMG Group Research Articles

P-695 Optimizing oocyte donor stimulation: A revelation from 2,666 cases emphasizing the sole efficacy of exogenous FSH

Abstract Study question Does the administration of human menopausal gonadotrophin in controlled ovarian stimulation improve clinical outcomes in the oocyte donation program? Summary answer The addition of hMG (human menopausal gonadotropin) reduces the number of retrieved oocytes without improving embryo development or clinical outcomes in oocyte donation program. What is known already In controlled ovarian stimulation for assisted reproduction treatments, follicle stimulating hormone(FSH) is essential, but the importance of LH supplementation from menopausal origin is controversial. It is a common practice to use hMG to provide the LH effect. The standard preparation contains FSH and LH effects in a 1:1 ratio.The FSH component would recruit ovarian follicles and stimulate their growth, while the LH component would facilitate their maturation. Our aim was to compare the outcomes of intracytoplasmic sperm injection (ICSI) treatments using a gonadotropin-releasing hormone GnRH) antagonist protocol with recombinant FSH(FSHr) alone and supplemented with hMG in the oocyte donation program. Study design, size, duration This is a retrospective cohort study of 2,666 patients enrolled in the oocyte donation program at a single center over four consecutive years. Donor stimulation commenced with daily FSHr injections. The FSHr group (n = 2,078) continued FSHr, while the FSHr+hMG group (n = 588) received hMG. Participants/materials, setting, methods Donors received GnRH agonist via i.m. injection until a mean diameter >18 mm in at least eight follicles. Transvaginal oocyte retrieval was scheduled 36h later, followed by ICSI for all retrieved oocytes. Embryos were cultured in time-lapse systems and evaluated using an artificial intelligence-based model (iDAScore v2). Recipients underwent hormone replacement therapy for endometrial preparation. Our comparative study examined oocytes retrieved, embryo score, implantation, and live birth outcomes in fresh and frozen embryo transfers (ETs). Main results and the role of chance The number of retrieved oocytes was higher in the FSHr group than in the FSHr+hMG group: 24.9±10.6 vs. 18.2±8.8 (p < 0.001). In addition, embryos from the FSHr+hMG group exhibited slower early development, with significantly lower division times to two, three, four and five cells in the FSHr group (p < 0.005). However, late parameters of embryo development showed no differences. Automatic scoring by the deep learning algorithm was identical for blastocysts in the FSHr (4.8±2.8) and FSHr+hMG groups (4.8±2.8); p = 1. Implantation rates showed no significant differences for fresh ET (FSHr: 58.6% vs. FSHr+hMG: 61.9%; n = 2,073; p = 1) or frozen ET (FSHr: 49.3% vs. FSHr+hMG: 46%; n = 2,687; p = 1). Similarly, there were no differences in live birth rates for fresh ET (FSHr: 45.6% vs. FSHr+hMG: 50.3%; n = 1,993; p = 1) or frozen ET (FSHr: 31.8% vs. FSHr+hMG: 33.8%; n = 2,508; p = 1). Limitations, reasons for caution The retrospective and single-center nature of the study would be its main limitations. It is essential to emphasize that these results are only applicable within the oocyte donation program. Wider implications of the findings Based on our findings, the use of exogenous FSHr alone is likely adequate in the GnRH antagonist protocol for optimal ovarian stimulation of donors, leading to the production of high-quality embryos and successful clinical outcomes. Trial registration number Not Applicable

#101 : A Direct Healthcare Cost Analysis of Recombinant LH Versus hMG Supplementation on FSH During Controlled Ovarian Hyperstimulation in the GnRH-Antagonist Protocol

Background and Aims: We have previous proposed a retrospective matched-case control study comparing the effect of recombinant LH versus hMG supplementation on FSH during COH in the GnRH-antagonist protocol. The result showed the cumulative live birth rate (CLBR) was significantly higher the in the LH group (53% vs. 64%, p=0.02). In this study we aim to do the cost analysis between these two groups based on our previous study. Method: The analysis consisted of 425 IVF and ICSI cycles performed in Taichung Veterans General Hospital, Taiwan between 2013 and 2018 in our previous study. They were chosen by Propensity score matching with balanced age, anti-mullerian hormone (AMH) level, and oocyte retrieval date. There were 259 cycles in hMG ± FSH group and 166 cycles in LH ± FSH group. The total cost related to treatment of each patient was recorded. Results: The treatment cost was showed in Table 1. The total treatment cost per patient was significantly higher in the LH than in the hMG group (USD 4194.93 ± 713.6 vs. $ 4466.33 ± 793.18 p=0.001). However, the mean costs per live birth in the hMG goup was higher with US $7875.42, vs. US $6928.83 in the LH group. The analysis of CLBR in the two groups in different treatment cost range results were showed in Figure 1 and Table 2. The CLBR was almost higher in the LH group in each range except for range between USD 5000-5499. When treatment cost between $4000-4499, the CLBR was significantly higher in the LH group than in the hMG group (81.8% vs. 54.3% p=0.006). Conclusions: The cost analysis showed that recombinant LH is more cost effectiveness than hMG supplementation on FSH during COH in the GnRH-antagonist protocol.

Letrozole cotreatment improves the follicular output rate in high-body-mass-index women with polycystic ovary syndrome undergoing IVF treatment.

Women who have polycystic ovary syndrome (PCOS) with high body mass index (BMI) typically have an attenuated ovarian response and decreased follicular size, which are linked to unfavourable clinical outcomes following in vitro fertilization (IVF) therapy. The follicular output rate (FORT), a qualitative indicator of follicular response, seems to be positively linked to the clinical outcomes of IVF. Progestin-primed ovarian stimulation (PPOS) has become an alternative to gonadotropin-releasing hormone (GnRH) analogues to inhibit the premature luteinizing hormone (LH) surge. As letrozole (LE) shows promise in enhancing ovarian response, we compared PPOS with and without LE for PCOS in high BMI women with a focus on the FORT and associated clinical and pregnancy outcomes. For the recruited 1508 women, ten variables including AFC; age; basal sex hormone level; BMI; infertility type; period of infertility and number of previous IVF attempts were chosen in the propensity score matching (PSM) model to match 1374 women who taken the MPA+ hMG protocol with 134 women who received the MPA+ hMG+ LE treatment at a 1:1 ratio. FORT was selected as the primary outcome measure. The number of oocytes retrieved, viable embryos, hMG dosage, duration, oocyte maturity rate, fertilization rate, and implantation rate were established as secondary outcomes. FORT was substantially elevated in the MPA+hMG+LE group compared with the MPA+hMG group (61% [35%, 86%] vs. 40% [25%, 60%], P <.001). Interestingly, the LE cotreatment group had a considerably lower mature oocyte rate despite having a similar number of mature oocytes and embryos recovered. The average hMG dosages and durations in the study group were similar to those in the control group. The implantation rate in the study group was numerically higher but without statistic significant than that in the control groups (43.15% (107/248) vs. 38.59% (115/298), OR 1.008, 95% CI 0.901-1.127; P >.05). The effect of LE combined with PPOS on FORT is better than the effect of the standard PPOS treatment in women with PCOS and a high BMI, but there is no substantially beneficial impact on pregnancy outcomes or the cycle features of COS, including consumption of hMG.

Investigation of isoflavone constituents from tuber of Apios americana Medik and its protective effect against oxidative damage on RIN-m5F cells

In our previous study, AI-3, a mixture of isoflavones, was obtained from Apios Americana Medik tuber and showed strong protective ability on oxidative damaged RIN-m5F cells. This study aimed to identify the main compounds of AI-3 and elucidate their activities and underlying mechanism. In results, eleven compounds were purified from AI-3. Among them, Compound 8 (2′-Hydroxy, 5-methoxy genistein-7-O-glucoside, HMG) was the most effective compound against H2O2-induced injury in RIN-m5F cells (stronger than positive control α-LA). Further RNA-seq analysis found that compared with H2O2 group, 388 differentially expressed genes (DEGs) were identified in HMG group. The enrichment analyses revealed fluid shear stress and atherosclerosis pathway and hepatocellular carcinoma pathway enriched the most DEGs, in which HOX-1, GST, NQO1, SQSTM, TrxR1 were significantly up-regulated. The finding indicated Keap1-Nrf2-ARE signaling pathway may play essential role in the protective effect of HMG on oxidative damaged RIN-m5F cells.

The comparison of two different protocols ultra-long versus medroxyprogesterone acetate in women with ovarian endometriosis: a prospective randomized controlled trial

BackgroundThis study aimed to investigate the medroxyprogesterone acetate (MPA) + HMG protocol vs ultra-long gonadotrophin releasing hormone (GnRH) agonist protocol in patients with advanced ovarian endometriosis who received in vitro fertilization (IVF).MethodsThree hundred patients with advanced ovary endometriosis who underwent IVF were included, and embryological and clinical outcomes were assessed between March 2017 and September 2017. Patients were divided into MPA + HMG group and 1-month ultra-long GnRHa protocol group.ResultsLower hMG dose and shorter medication time were found in the MPA + HMG group than in the GnRHa group (P < 0.05). Follicle to-Oocyte Index was significantly different between MPA + HMG group and GnRHa group (P < 0.001). No differences were found in the ovary response and numbers of mature oocytes, fertilized oocytes and viable embryos. The clinical pregnancy and live birth outcomes were similar between MPA + HMG group and GnRHa group, and these outcomes were independent of fresh or frozen embryo transfer in the GnRHa protocol group. There were no significant differences in the time to embryo transfer, medical cost and adverse effects.ConclusionThe number of oocytes retrieved and pregnancy outcomes after MPA + HMG protocol are similar to those after ultra-long GnRHa protocol in women with ovarian endometriosis. MPA + HMG protocol may be an alternative to ultra-long GnRHa protocol for IVF in ovary endometriosis patients.Trial registration The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INR-17010924)Plain English summaryIn conclusion, the administration of MPA in COH showed similar number of oocytes retrieved, no premature LH surge, and similar pregnancy and live birth outcomes in patients with advanced ovarian endometriosis undergoing IVF/ICSI as compared to the one-month long protocol. The use of MPA in COH appears to be promising although many questions remain to be elucidated, including the dose and time of progestin priming as well as its possible influence on the oocyte development potential and microenvironment. Given their good tolerability, few metabolic influence, and low cost, progestogens provide a novel alternative to the conventional protocol for patients with endometriosis.

A retrospective, matched case-control study of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

BackgroundThe role of luteinizing hormone (LH) in controlled ovarian hyperstimulation (COH) requires more evidence for its efficacy. Several studies compared recombinant human LH (r-hLH) or human menopausal gonadotropin (hMG) in combination with recombinant human follicle-stimulating hormone (r-hFSH) but lack the results with GnRH-antagonist protocol and in Asians.MethodsThis is a retrospective, single-center study inspecting women receiving GnRH antagonist protocol and r-hFSH+hMG or r-hFSH+r-hLH regimen for over five days for COH in the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle in Taiwan from 2013 to 2018. The outcomes of IVF/ICSI cycles were analyzed after propensity score matching between the two groups. A subgroup analysis was conducted in cycles in which women underwent their first embryo transfer (ET), including fresh ET and frozen ET (FET).ResultsWith a total of 503 cycles, the results revealed that the r-hFSH+r-hLH group performed better in terms of numbers of oocytes retrieved (r-hFSH+hMG vs. r-hFSH+r-hLH, 11.7 vs. 13.7, p=0.014), mature oocytes (8.7 vs. 10.9, p=0.001), and fertilized oocytes (8.3 vs. 9.8, p=0.022), while other outcomes were comparable. The analysis of first ET cycles also showed similar trends. Although the implantation rate (39% vs. 43%, p=0.37), pregnancy rate (52% vs. 53%, p=0.90), and live birth rate (39% vs. 45%, p=0.19) were not significantly different, the miscarriage rate was higher in the r-hFSH+hMG group than the r-hFSH+r-hLH group (26% vs. 15%, p<0.05) in first ET cycles. The cumulative pregnancy rate was significantly higher in the r-hFSH+r-hLH group (53% vs. 64%, p=0.02). No significant difference in rates of ovarian hyperstimulation syndrome (OHSS) was observed.ConclusionThe results support the hypothesis that the treatment of r-hLH+r-hFSH improves COH clinical outcomes in the IVF/ICSI cycle.

P-597 The effects of triple trigger on IVF outcomes and pregnancy rates in poor responder patients

Abstract Study question Are there any positive effects of triple trigger on oocyte morphology, embryo quality and pregnancy rates in poor responder (POR) patients? Summary answer The trigger with human chorionic gonadotropin (hCG), gonadotropin-releasing hormone agonist (GnRHa) and human menopausal gonadotropin (hMG) may improve embryo quality and pregnancy rates in POR. What is known already The ESHRE consensus criteria define a poor ovarian response (POR) as less than four oocytes retrieved. Advanced female age and severe sperm disorder were associated fertilization failure after intracytoplasmic sperm injection (ICSI). Also, oocyte quality is pivotal to determine the fertilization of the oocyte. Hence there is no study to evaluate triple trigger on the embryo quality in POR and severe male infertility are excluded. Study design, size, duration In this prospective randomized study, we analyzed poor responder patients that have history of fertilization failure and cleavage arrest embryo, including 100 patients with only hCG trigger (group 1), 100 patients with dual trigger hCG + GnRHa (Group 2), and 100 patients with triple trigger hCG + GnRHa + hMG (Group 3). Patients who have the POR criteria according to MII oocytes lower than 4 were included in the analysis. Participants/materials, setting, methods Mean age, body mass index (BMI), AMH levels, day-2 FSH and E2, duration of infertility, LH and E2 levels on trigger day, duration of stimulation, total dose of gonadotropins used, number of previous trials, MII oocytes were examined and compared between the groups. Sperm concentration under 5 x 106 mL was not included to exclude severe male factor. Embryo quality, pregnancy rates evaluation was performed for each patient that has been performed GnRH antagonist protocols. Main results and the role of chance Age, Body Mass Index (BMI), AMH levels, day 2 FSH and E2, duration of infertility, duration of stimulation, E2 levels on trigger day, and total dose of gonadotropins usage between the three groups were similar. Number of MII oocytes, fertilization (2PN), and D5 (blastocyst) embryo transfer were significantly higher in Group 3 (Table 1). Pregnancy rates are higher in group 3 however significantly not significant. Limitations, reasons for caution The study is limited by its sample size and a higher sample size might be used in the future studies to corroborate the current findings. hMG trigger dosage may be arranged in another study. Wider implications of the findings Our results showed that the number of MII oocytes 2PN levels, D5 ET were higher in DOR patients triggered with hCG + GnRHa + hMG. Trial registration number 28012022

P-621 Different gonadotrophins adopted for controlled ovarian stimulation do not affect metaphase-II oocyte competence. A matched case-control study on 351 patients and 2258 oocytes

Abstract Study question Do different gonadotrophins for controlled-ovarian-stimulation (COS) affect metaphase-II (MII) oocyte competence? Summary answer Euploid blastocyst rate (EBR) per cohort of MII-oocytes, live-birth-rate (LBR) per first vitrified-warmed euploid single-embryo-transfer (SET) and cumulative-LBR are independent from the gonadotrophins used. What is known already Controlled-ovarian-stimulation (COS) is a cornerstone of IVF. Its purpose is maximizing ovarian reserve exploitation and obtaining ≥1 euploid blastocyst to transfer. Indeed, ovarian reserve decreases and blastocyst aneuploidy rates increase with increasing maternal age, making this task quite complicated in advanced maternal age. Old-fashioned studies suggested an association between COS and embryonic aneuploidy rates. Conversely, recent studies excluded an impact of COS dosage, duration, ovarian response, and ovulation trigger, on blastocyst aneuploidy rate. An aspect, though, needs more clarity: do different gonadotropins impact oocyte competence after COS, comprehensively defined as EBR per cohort of MII-oocytes? Study design, size, duration Out of 3169 PGT cycles with ³1 MII oocyte conducted between 2014-2018, we excluded (i)PGT-M/-SR, (ii)women&amp;lt;35yr, (iii)severe-male-factor, (iv)DuoStim or long-active FSH, (v)culture with sequential-media, and (v)multiple cycles. Among the 784 cycles left, a propensity-score-matching (PSM) based on the number of inseminated MII-oocytes was adopted to match patients using recFSH [without (N = 57; 337 MII-oocytes)/with recLH (N = 55; 374 MII-oocytes)] and Human-Menopausal-Gonadotrophin (HMG; N = 127; 835 MII-oocytes). The patients using recFSH+HMG were all included (N = 112; 712 MII-oocytes). Participants/materials, setting, methods Only GnRH-antagonist COS, ICSI with fresh MII-oocytes, single culture in continuous-media, trophectoderm biopsy without assisted-hatching, comprehensive-chromosome-testing to assess full-chromosome non-mosaic aneuploidies and vitrified-warmed euploid SET were conducted. Oocyte competence was comprehensively defined as EBR per cohort of MII-oocytes with all intermediate outcomes (fertilization, blastulation and euploidy). LBR per first vitrified-warmed euploid SET and cumulative-LBR per retrieval were also assessed. Generalized-linear-models and multivariate regressions were adopted to adjust the results for confounders. All cycles were concluded. Main results and the role of chance Patients using recFSH+recLH and recFSH+HMG (40.7 yr) were older than patients using recFSH-only or HMG-only (40 yr; ANOVA&amp;lt;0.01). No other difference was reported in the 4 patient populations. The overall gonadotrophins dosage (2615±977, 3601±1889, 3818±946 and 2892±911 IU in the recFSH-only, recFSH+recLH, recFSH+HMG and HMG-only groups, respectively) and duration of COS (9.7±1.9, 9.4±1.5, 9.9±1.8 and 10.2±1.8 days) were different (Kruskal-Wallis tests=0.02). The number of cumulus-oocyte-complexes (9.2±6.5) and MII-oocytes collected (6.4±4.4) were instead well-matched across the groups. The EBR per cohort of inseminated MII-oocytes was different in the four groups (20.7±27.1%, 9.6±12.9%, 12.4±18.5% and 16.9±21.8%, respectively), but, when adjusted for maternal age in a generalized-linear-model, the gonadotrophin used for COS did not show any significant association with this outcome (partial-eta2=0.02, p = 0.1, power=0.6). All intermediate embryological outcomes were also similar. The LBR per first vitrified-warmed euploid SET was comparable in the four groups [N = 14/33 (42%), N = 9/22 (41%), N = 26/62 (45%), N = 24/55 (44%), respectively], as confirmed by the logistic regression adjusted for blastocyst quality (multivariate-OR: 0.97, 95%CI 0.73-1.31, adjusted-p=0.9). Lastly, the cumulative-LBRs per retrieval were equivalent [N = 17/57 (30%), N = 14/55 (26%), N = 34/127 (27%), and N = 33/112 (30%), respectively], as confirmed by the logistic regression adjusted for maternal age (multivariate-OR: 1.01, 95%CI 0.8-1.3, adjusted-p=0.9). Limitations, reasons for caution The gonadotrophins were chosen based on patient compliance to their administration route and gynecologist judgement, and only qualitative outcomes were assessed. Therefore, randomized-controlled-trials and cost-effectiveness analysis investigating the efficiency in oocyte recruitment and cumulative-LBR per intention-to-treat are needed. Wider implications of the findings Different gonadotrophins might not affect MII-oocyte competence. This information is key since, in view of the optimization of follicle recruitment through personalized-COS, it allows more flexibility in the choice of the most suitable protocol. Therefore, gynecologists might ponder also features like patient reproductive history and compliance to different administration routes. Trial registration number none

A RETROSPECTIVE COMPARISON OF IVF-ET OUTCOMES IN THOSE USING FOLLITROPIN-Δ AND FOLLITROPIN-Α IN ROUTINE CLINICAL PRACTICE

Follitropin-Δ (Rekovelle ®[REK], Ferring Pharmaceuticals) is a recombinant gonadotropin (Gn) produced by human, fetal retinal cell line with a glycosylation pattern similar to native human FSH. Based on differing bioavailability and efficacy to follitropin-α (rFSH), it is the first Gn to use a personalized dosing algorithm based on anti-Müllerian hormone (AMH) and body weight to achieve a predictable and optimal ovarian response (8 to 14 oocytes). We evaluated the efficacy of REK in the clinical practice setting when used alone or in combination with human menopausal (hMG) Gn. Retrospective analysis of all cycles performed by a single provider between January 2020 to January 2021. REK and rFSH were not selected by specific criteria. HMG was added to expected poor responders. All cycles included that progressed to oocyte collection were analyzed with respect to cycle stimulation, laboratory, and ongoing (OG) pregnancy outcomes. Group comparisons included REK +/- hMG vs. rFSH +/- hMG and were performed using chi square and student t-test as appropriate. Table depicts demographic, cycle stimulation, and clinical outcomes between groups. No differences in baseline demographics, number of MII oocytes, fertilization/MII oocyte, and % of good quality embryos were noted. However, REK +/- hMG resulted in significantly lower daily and total Gn used, while more cycles resulted in an optimal range response, though this failed to achieve significance. Low and high response were less likely in the REK +/- hMG groups (low: 36.9% vs. 46.6%; high: 10.8% vs. 14.4%); though differences not significant. The fresh OG pregnancy rates/ET and cumulative OG pregnancy rates/patient were similar between groups.Tabled 1REK +/- hMG (n=46)rFSH +/-hMG (n=236)p valueAge (yrs)35.9 ± 3.536.7 ± 4.40.24BMI (kg/m2)23.0 ± 3.922.7 ± 3.50.76AMH (ng/ml)1.93 ± 1.02.59 ± 3.30.21Daily Gn Dose (IU)173 ± 69215 ± 830.001Total Gn dose (IU)1783 ± 7082229 ± 9250.002Days of stimulation10.4 ± 1.510.3 ± 10.50.85Number of oocytes8.9 ± 4.18.9 ± 5.50.99Number of MII6.3 ± 4.36.0 ± 4.10.69Optimal range response (%)52.2 (24/46)38.5 (91/236)0.14Fertilization/MII oocyte (%)81 ± 2478 ± 270.46% of good quality embryos49 ± 3049 ± 320.85Fresh ET (%)82.681.20.89Fresh OG/ET (%)23.725.40.82Cumulative OG/ per patient (%)35.530.60.23 Open table in a new tab While follitropin-Δ appears to result in similar clinical outcomes to follitropin-α, it produces more in range responses while using less total dosing in the clinical setting.

EMBRYOS MORPHOKINETICS: DOES THE SOURCE OF GONADOTROPHIN PREPARATIONS MATTER?

Follicle growth can be obtained with different preparations or combinations of gonadotrophins. Approaches combining FSH with LH-like-action gonadotrophins have been associated with improved IVF outcomes. Whether a controlled ovarian stimulation (COS) regimen based on r-FSH and r-LH leads to better outcomes compared with a protocol using human menopausal gonadotropin (hMG) is still under debate. The goal for the present study was to compare the effect of two FSH plus LH-like protocols on morphokinetic events in a time-lapse imaging (TLI) system. This retrospective cohort study was performed in a private university-affiliated IVF center from March 2019 to December 2020 and included 1268 embryos, cultured in a TLI incubator, from 198 ICSI cycles. Cycles were split into two groups depending on the protocol applied for COS: 142 patients (904 embryos) were stimulated with rFSH + rLH, whereas 56 patients (364 embryos) were treated with hMG. The effects of the COS protocol on morphokinetic events and ICSI outcomes were compared among the groups taking into account clustering of data (multiple embryos per cycle), using generalized mixed models. Evaluated kinetic markers were: pronuclei appearance (tPNa), timing to pronuclei fading (tPNf), timing to two (t2), three (t3), four (t4), five (t5), six (t6), seven (t7), and eight cells (t8), and timing to start of blastulation (tSB) and to blastulation (tB). Durations of the second (t3-t2) and third (t5-t3) cell cycles (cc2 and cc3, respectively) and timing to complete synchronous divisions s1 (t2-tPNf), s2 (t4-t3), and s3 (t8-t5) were also evaluated. The post hoc achieved power was > 99.0%. When compared with the protocol with hMG, COS using rFSH + rLH leaded to faster tPNa (7.4h ± 0.30 vs 6.5h ± 0.18, p<0.007), tPNf (25.6h ± 0.40 vs 24.4h ± 0.25, p<0.009), t5 (50.0h ± 0.60 vs 48.5h ± 0.37, p<0.035), and t6 (52.9h ± 0.58 vs 51.5h ± 0.37, p<0.043). The s3 were also decreased in rFSH + rLH protocols (10.4h ± 0.36 vs 8.9h ± 0.58, p<0.033). As for the clinical outcomes, no significant differences were noted among the groups for pregnancy (40.0% ± 11.0 vs 33.0% ± 10.9, p=0.398) and implantation rates (28.0% ± 6.2 vs 22.2% ± 8.4, p=0.76), for rFSH + rLH and hMG groups respectively. Stimulation protocols using associations of rFSH and rLH lead to faster initial embryo development when compared with protocols using hMG.

Supplementation with human menopausal gonadotropin in the gonadotropin-releasing hormone antagonist cycles of women with high AMH: Pregnancy outcomes and serial hormone levels

ObjectiveTo evaluate the value of using both HMG and recombinant FSH (r-FSH) in the GnRH antagonist protocol for women with high AMH. Materials and methodsThis retrospective, single-center cohort study was conducted from January 2013 to December 2018. Of 277 GnRH antagonist IVF/ICSI cycles in women with anti-Mullerian hormone (AMH) ≥5 μg/L, 170 cycles receiving the combination of r-FSH and HMG (77 with HMG added at the beginning of the GnRH antagonist cycle and 93 with HMG added after GnRH antagonist administration) and 107 cycles receiving r-FSH alone were analyzed. The dynamic hormone profiles and embryonic and clinical outcomes of the patients were evaluated. ResultsWe observed significantly lower serum LH levels in the r-FSH + HMG groups during ovarian stimulation. The serum estradiol and progesterone levels were lower in the r-FSH + HMG groups on the trigger day. Nevertheless, there were no significant differences with respect to the number of oocytes retrieved, maturation, fertilization, blastocyst formation rate or ovarian hyperstimulation syndrome (OHSS). The implantation and live birth rates were increased in the r-FSH + HMG groups compared with the r-FSH alone group, with no statistical significance. ConclusionsHMG for LH supplementation in the GnRH antagonist protocol for patients with high AMH is not significantly superior to r-FSH alone in terms of ovarian response and pregnancy outcome. Nevertheless, HMG supplementation might be appropriate for women with an initially inadequate response to r-FSH or intracycle LH deficiency.

Clinical effect of adding hMG to the follicular phase long protocol for standard group with normal ovarian reserve function

Objective: To investigate the impact of adding human menopausal gonadotropin (hMG) for in vitro fertilization-embryo transfer pregnancy outcomes in a standard population of non-advanced age with normal ovarian reserve function using a long follicular phase protocol. Methods: Clinical data of 489 patients with normal ovarian reserve function, who were admitted from January 2018 to January 2020 in the Affiliated Hospital of Guizhou Medical University and underwent in vitro fertilization for the first time with the long follicular phase protocol in fresh cycles, were retrospectively analyzed. The patients were divided into three groups according to whether or not to add urine-derived hMG and the timing of addition: non-addition group (group A), medium-term hMG group (group B1), whole course hMG group (group B2); the laboratory parameters of each group were observed, and the effect of ovulation induction drugs and pregnancy outcomes were compared. Results: The ages of B1 and B2 groups were significantly higher than that of group A (P=0.019 and P=0.011). The basal FSH level of group B2 was significantly higher than those of group A and group B1 (P<0.01 and P=0.006), and the basal FSH/LH ratio of group B2 was significantly higher than that of group B1 (P=0.009). Antral follicle counts of group A and group B1 were significantly higher than that of group B2 (P=0.007 and P=0.017). The superior embryo rate of group B2 [(47±27)%] was significantly higher than that of group A (P=0.017). The embryo implantation rate of group B1 was significantly lower than those of group A and group B2 (P=0.043 and P<0.01). The clinical pregnancy rate of group B2 [76.7% (155/202)] was significantly higher than those of group A (P=0.039) and group B1 (P<0.01). The live-birth rate of group B2 [67.3% (136/202)] was significantly higher than those of group A (P=0.017) and group B1 (P=0.001). Conclusions: For non-advanced aged patients with normal ovarian reserve function, the long protocol of follicular phase is suitable for those with relatively low ovarian reserve function. Adding hMG in the whole course of ovulation induction after gonadotropin-releasing hormone agonist reduction could improve the pregnancy outcomes by improving the quality of embryos.

Predictors of pregnancy after intrauterine insemination in women with polycystic ovary syndrome.

ObjectiveTo evaluate the effects of body mass index (BMI) in patients with polycystic ovary syndrome (PCOS) undergoing controlled ovarian stimulation (COS) with intrauterine insemination (IUI).MethodsThis retrospective study evaluated couples with PCOS undergoing COS and IUI. The relationship between cumulative IUI pregnancy outcomes and BMI, treatment cycles, treatment schemes, number of dominant follicles, endometrial thickness, infertility duration and type of infertility was analysed.ResultsThe study evaluated 831 IUI cycles in 451 couples with PCOS. Compared with normoweight women, overweight and obese women required more human menopausal gonadotropin (hMG) doses and more days of COS. Gestational diabetes mellitus occurred more frequently in the obese group than in the other BMI groups. The clinical pregnancy and live birth rates in the hMG, clomiphene citrate (CC) + hMG and letrozole (LE) + hMG groups were significantly higher than those in the CC and LE groups. The clinical pregnancy rate was higher in the secondary infertility group compared with the primary infertility group.ConclusionObese women might require more hMG doses and more days of COS to overcome the effects of weight. As BMI increases, the incidence of gestational diabetes might also increase. The number of cycles and type of infertility may have a predictive value for pregnancy outcomes.

Human Menopausal Gonadotropin Commenced on Early Follicular Period Increases Live Birth Rates in POSEIDON Group 3 and 4 Poor Responders.

Human menopausal gonadotropin (hMG) has LH activity, and it may have beneficial effects in terms of oocyte quality and endometrial receptivity similar to recombinant LH supplementation. The aim of this study was to assess the effects of hMG, and its commencement time on the outcome of assisted reproductive technology (ART) cycles of POSEIDON group 3 and 4 poor responders. Data of 558 POSEIDON group 3 and 4 poor responders who underwent ART treatment following a GnRH antagonist cycle at a university-based infertility clinic between January 2014 and December 2019 were reviewed. hMG was commenced at the early follicular phase or mid-follicular phase in the study groups. The control group did not receive hMG stimulation. Live birth rate (LBR) was the main outcome measure. The mean duration of stimulation was significantly shorter in early follicular hMG group than in mid-follicular hMG group (11.9 ± 3.6days vs. 12.8 ± 4days, respectively; P = 0.027). The mean numbers of oocytes retrieved and MII oocytes were comparable between the groups. The LBRs per embryo transfer in early follicular hMG, mid-follicular hMG, and control groups were 21.9%, 11.7%, and 11.6%, respectively (P = 0.035). In conclusion, there is a significant association between the commencement time of hMG and live birth chance in ART cycles of POSEIDON group 3 and 4 poor responders. Early initiation of hMG together with rFSH seems to be beneficial in this specific population.

The addition of clomiphene citrate to ovarian stimulation protocols for poor responders

Poor ovarian response (POR) is one of the most challenging problems in assisted reproduction. Several strategies have been used to improve pregnancy rates. The use of Clomiphene Citrate (CC) has been shown to improve ovarian stimulation outcomes and decrease gonadotropin requirements in women of advanced reproductive age. However, the combination of CC and gonadotropins to improve pregnancy rates after in IVF in poor responders is still unexplored due to the small number of trials with few participants.This is a prospective cohort trial involving 12 patients diagnosed with poor ovarian response who underwent ovarian stimulation during the period between June 2015 and September of 2017. All patients were treated with the maximum dose of gonadotropins (hMG, 300 IU/day, hMG group) according to a short gonadotropin/GnRH antagonist protocol. In a subsequent cycle those patients underwent the same stimulation protocol with the addition of 100 mg of CC from day 3 to day 7 (CC-hMG group).Supplementation with 100 mg of CC resulted in a statistically significant increase in estradiol levels, number of follicles and number of oocytes retrieved, as well as an increase in the number of total embryos available for transfer. Furthermore, a significant reduction was observed in cancellation rates in the CC-hMG group. Two clinical pregnancies, which resulted in two live births and 3 biochemical pregnancies were achieved in the CC/hMG group.Furthermore, by employing open-source, biological data we identified a common gene (Estrogen Receptor 1, ESR1) between genetic targets of clomiphene treatment and POR which could explain the benefits of clomiphene in this group of patients.In conclusion, the addition of CC 100 mg to the stimulation regimen in women diagnosed with POR and previous failed IVF cycles could improve stimulation results, but this study could not demonstrate any benefit in terms of clinical pregnancies and live births. The effectiveness of this treatment requires further investigation.

Efficacy of Different Progestins in Women With Advanced Endometriosis Undergoing Controlled Ovarian Hyperstimulation for in vitro Fertilization-A Single-Center Non-inferiority Randomized Controlled Trial.

Object: Is it possible to use different progestins cotreatment with human menopausal gonadotrophin (hMG) in women with advanced endometriosis but normal ovulation during controlled ovarian hyperstimulation (COH) in vitro fertilization (IVF)? Whether different progestins treatments can be an alternative choice for women with severe endometriosis in considering IVF/ICSI treatment remains unknown?Design: Non-inferiority randomized clinical trial.Setting: Tertiary-care academic medical center.Population: Four hundred and fifty infertile patients with severe endometriosis undergoing IVF/ICSI between May 2016 and March 2017.Methods: Four hundred and fifty infertile patients with severe endometriosis undergoing IVF/ICSI were randomized to: medroxyprogesterone acetate +hMG; dydrogesterone +hMG; and progesterone +hMG. Ovulation was induced with a gonadotropin-releasing hormone agonist (GnRH-a) and chorionic gonadotropin (hCG). Viable embryos were cryopreserved for later transfer.Main Outcome Measures: The primary endpoint outcome was the number of oocytes retrieved. Secondary indicators included the incidence of a premature surge in luteinizing hormone (LH), the number of viable embryos, and clinical pregnancy outcomes.Results: The number of oocytes retrieved was higher in the medroxyprogesterone acetate +hMG group than the two other groups (9.3 ± 5.7 vs. 8.0 ± 4.5 vs. 7.8 ± 5.2, P = 0.021). LH levels were suppressed after a 6-day progestin treatment in the medroxyprogesterone acetate +hMG and dydrogesterone +hMG groups, but there was a rebound of LH values in the progesterone +hMG group. No premature LH surge and ovarian hyperstimulation syndrome (OHSS) occurred. No significant differences among the three groups were observed in fertilization and pregnancy outcomes.Conclusion: It is mandatory to point out that our conclusions are valid for patients with ovarian advanced endometriosis but normal ovarian functions. These results suggest three different progestins protocols are equivalent in terms of pregnancy outcomes for women with advanced endometriosis. PPOS protocol can be an alternative choice for women with severe endometriosis and normal ovarian reserve in IVF/ICSI treatment. These methods could be tested with other populations of women with endometriosis.Clinical Trial Registration: www.ClinicalTrials.gov, identifier:ChiCTR-OIN-16008529.Trial registration date: 2014-05-25.Date of first patient enrollment: May 2016

Efficacy of follitropin-alpha versus human menopausal gonadotropin for male patients with congenital hypogonadotropic hypogonadism.

To compare human menopausal gonadotropin (hMG) and recombinant follicle-stimulating hormone (rFSH) with respect to successful spermatogenesis and pregnancy outcomes in patients with congenital hypogonadotropic hypogonadism (CHH). This retrospective study included a total of 112 male patients with CHH. Of these, 70 were to receive treatment with hMG and 42 with rFSH following the hCG administration. The average age at diagnosis was 27.9 (range, 15-51) years. The baseline luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were 0.53±0.77 IU/L, 0.63±0.61 IU/L, and 1.10±1.90 ng/dL, respectively. Following the combined hormonal treatment, 85.7% (96/112) of patients had sperm detected in ejaculate samples. In the hMG group, the mean baseline of a testicular size was slightly lower than in the rFSH group (5.0±3.5 mL and 5.3±3.9 mL), whereas these differences were not statistically significant (p=0.364). The mean baseline age, level of FSH, LH, and testosterone also showed no significant difference between the two treatment options. The rate of successful spermatogenesis was similar (85.7%) in both groups, while the pregnancy rates of patients who underwent hMG and rFSH treatments were 38.6% (n=27) and 51.2% (n=21); however, these differences were not statistically significant (p=0.314). No patients developed severe effects during the treatment period. Successful spermatogenesis and pregnancy rates with hMG and rFSH are similar.

Progestin-Primed Ovarian Stimulation with Dydrogesterone versus Medroxyprogesterone Acetate in Women with Polycystic Ovarian Syndrome for in vitro Fertilization: A Retrospective Cohort Study.

PurposeDydrogesterone (DYG) is an alternative progestin in progestin-primed ovarian stimulation (PPOS) protocol with weaker pituitary suppression than medroxyprogesterone acetate (MPA) in normal ovulatory women. However, the endocrinological characteristics, oocyte retrieval and pregnancy outcomes of DYG application in polycystic ovarian syndrome (PCOS) patients undergoing in vitro fertilization (IVF) remain unclear.Patients and methodsThis retrospective cohort study included 420 PCOS patients who underwent controlled ovarian stimulation with human menopausal gonadotropin (hMG) and DYG (n=105) or MPA (n=315) from January 2014 to December 2017. Baseline characteristics of the two groups were balanced with propensity score matching using the nearest-neighbor random matching algorithm in a ratio of 1:3. The primary outcome measure was the number of oocytes retrieved. Other main outcome measures included the number of viable embryos, incidence of premature luteinizing hormone (LH) surge and live birth rate per frozen-thawed embryo transfer (FET) cycle.ResultsA similar number of oocytes was retrieved in the two protocols (16.1±6.5 vs 15.1±10.0, P=0.342). Patients in both groups achieved consistent LH suppression with no premature LH surge detected. In the DYG + hMG group, the mean LH levels were significantly higher than the MPA + hMG group on cycle day 9–11 and trigger day (all P<0.001), and the dose of hMG was significantly lower (1710.7±431.6 vs 1891.3±402.2 IU, P<0.001). No significant between-group differences were found in the number of viable embryos (5.3±3.1 vs 5.0±4.1, P=0.139) and live birth rate per FET cycle (43.5% vs 47.7%, P=0.383). None of the participants experienced moderate-to-severe ovarian hyperstimulation syndrome in either group.ConclusionOur results showed that the application of DYG in PPOS protocol could achieve comparable oocyte retrieval and pregnancy outcomes to MPA, but significantly reduce the consumption of gonadotropins in PCOS women for IVF treatment.

Coculture of porcine cumulus-oocyte complexes with porcine luteal cells during IVM: effect on oocyte maturation and embryo development.

Coculture with somatic cells is an alternative to improve suboptimal invitro culture conditions. In pigs, IVF is related to poor male pronuclear formation and high rates of polyspermy. The aim of this study was to assess the effect of a coculture system with porcine luteal cells (PLCs) on the IVM of porcine cumulus-oocyte complexes (COCs). Abattoir-derived ovaries were used to obtain PLCs and COCs. COCs were matured invitro in TCM-199 with or without the addition of human menopausal gonadotrophin (hMG; C+hMG and C-hMG respectively), in coculture with PLCs from passage 1 (PLC-1) and in PLC-1 conditioned medium (CM). In the coculture system, nuclear maturation rates were significantly higher than in the C-hMG and CM groups, but similar to rates in the C+hMG group. In cumulus cells, PLC-1 coculture decreased viability, early apoptosis and necrosis, and increased late apoptosis compared with C+hMG. PLC-1 coculture also decreased reactive oxygen species levels in cumulus cells. After IVF, monospermic penetration and IVF efficiency increased in the PLC-1 group compared with the C+hMG group. After invitro culture, higher blastocysts rates were observed in the PLC-1 group. This is the first report of a coculture system of COCs with PLCs. Our model could be an alternative for the conventional maturation medium plus gonadotrophins because of its lower rates of polyspermic penetration and higher blastocysts rates, key issues in porcine invitro embryo production.

Randomized controlled trial comparing embryonic quality in rFSH versus hMG in the IVF protocol with GnRH Antagonist.

Objective:The aim of the present study is to investigate embryo quality (score) after controlled ovarian stimulation for IVF using rFSH or hMG with the GnRH antagonist protocol.Methods:Open, randomized, single center study. The patients were randomized to receive rFSH or hMG according to randomized cards inside a black envelope with the name of the respective treatment following a computer generated list (85 patients were allocated to rFSH group and 83 patients to hMG group). Inclusion criteria were patients with IVF indication and normal ovarian reserve. Embryo evaluation was performed on day three, after fertilization based on the Graduated Embryo Score (GES).Results:There were no relevant differences in demographic characteristics. There was no difference in pregnancy rates with 27 (31%) and 25 (30.1%) pregnancies for rFSH and hMG, respectively (p=0.87). The total embryo score was the same for both groups, but the best embryo score was significant higher for the rFSH group (77.33±34.0 x 65.07±33.2 p=0.03). The total number of embryos was statistical different, also in favor of the rFSH group (4.17±3.1 x 3.26±2.4 p=0.04).Conclusion:The total embryo score was the same for both groups, but the best embryo score was significantly higher for the rFSH group. Moreover, rFSH was associated with an increased number of embryos.