Total Gonadotropin Research Articles

A randomized, non-inferiority trial on the DuoStim strategy in PGT-A cycles

Research questionIs the DuoStim strategy an effective alternative to two conventional ovarian stimulation cycles in poor-prognosis patients undergoing preimplantation genetic testing for aneuploidies (PGT-A) to improve euploidy rates and obtain the first euploid embryo in less time? DesignThis randomized controlled trial was performed at IVI Madrid between June 2017 and December 2020 and included 80 patients with a suboptimal profile aged 38 or older undergoing PGT-A cycles. Patients were blindly randomized into two groups: 39 women underwent two ovarian stimulations in consecutive cycles (control group), whereas the double stimulation strategy was applied to 41 women (DuoStim group). The main outcome was the euploidy rate in each group. The secondary outcomes were the time it took to obtain a euploid embryo and the main cycle outcomes. ResultsThe baseline characteristics of the patients were similar. No differences were found between the control group and the DuoStim group in the mean days of stimulation (21.3 ± 1.6 versus 23.0 ± 1.4, P = 0.10), total gonadotrophins (4005 ± 450 versus 4245 ± 430, P = 0.43), metaphase II oocytes (8.7 ± 1.8 versus 6.8 ± 1.7, P = 0.15) or euploid embryos obtained (0.8 ± 0.4 versus 0.6 ± 0.4, P = 0.45). The euploid rate per randomized patient (ITT) was 16.1% in the control group versus 22.7% in the DuoStim group, with P-values of 0.371, and the euploidy rate per patient treated was 39.0% versus 45.7% in the control versus DuoStim groups. However, there was a significant difference in the average number of days it took to obtain a euploid blastocyst, favouring the DuoStim group (44.1 ± 2.0 versus 23.3 ± 2.8, P < 0.001). ConclusionsThe use of the DuoStim strategy in poor-prognosis patients undergoing PGT-A cycles maintains a similar euploidy rate while reducing the time required to obtain a euploid blastocyst.

The earlier the initiation of gonadotropin in poor responders in luteal phase stimulation protocols, the better.

Luteal-phase ovarian stimulation has been proved to be feasible for producing competent oocytes/embryos and achieving live births, yet there is no standardized stimulation protocol for luteal-phase ovarian stimulation (LPS). The aim of this study was to explore the optimal timing of gonadotropin initiation in the LPS protocol for poor ovarian responders. This was a retrospective cohort study conducted in the reproductive medicine center of a tertiary hospital. A total of 327 poor responders fulfilling Bologna criteria underwent LPS with IVF/ICSI treatment. HMG and letrozole were administrated after ovulation. Patients were stratified into three groups according to the gonadotropin start day: early, early-mid, and mid-late luteal phase. A freeze-all strategy was performed for all cycles. The duration of ovarian stimulation, total gonadotropin dose, number of oocytes retrieved, implantation rate, clinical pregnancy rate, and live birth rate after frozen/thawed embryo transfer cycles were included for evaluation. The group accepted ovarian stimulation in the earlier phase tended to have a shorter duration of ovarian stimulation [8 (7,10) in early luteal group, 9 (8,10.25) in early-mid luteal group, and 11 (10,12) in mid-late luteal group; P <0.001] and lower gonadotropin consumption [1993.35 ± 720.31, 2282.73 ± 703.38, and 2764.83 ± 722.26, respectively; P <0.001]. Logistic regression and multiple linear regression were used to assess the associations between the phase of gonadotropin initiation and duration of ovarian stimulation (or total gonadotropin dose) by adjusting for confounding factors. Compared with the early luteal group, longer ovarian stimulation(>9 days) was more likely to occur in the early-mid and mid-late luteal groups, with the adjusted odds ratios 0.584 (0.327-1.042) and 0.116 (0.049-0.271), respectively (P-trend<0.001). Delayed gonadotropin initiation showed an 113.200 IU increase (95%CI: 70.469, 155.930) per-day in the total gonadotropin dosage. Meanwhile, there were no significant differences in the mean number of oocytes, utilizable embryos, pregnancy outcomes among three groups. Although the timing of gonadotropin initiation is not associated with pregnancy outcomes, earlier initiation of gonadotropin therapy after ovulation was associated with a shorter duration of ovarian stimulation and lower gonadotropin consumption in poor responders in LPS.

The impact of oocytes containing smooth endoplasmic reticulum aggregates on assisted reproductive outcomes: a cohort study

BackgroundThe impact of smooth endoplasmic reticulum aggregates (SERa) on assisted reproductive technology (ART) outcomes was still controversial. Our objective is to investigate the impact of the presence of SERa on intracytoplasmic sperm injection (ICSI) outcomes.MethodsThis was a retrospective cohort study. A total of 1,090 fresh ICSI cycles from 944 patients between January 2016 and June 2020 were included. Outcomes from clinical, embryological and neonatal aspects were compared between SERa + and SERa- cycles as well as between SERa + and SERa- oocytes.ResultsThe total gonadotropin (Gn) dose, number of oocytes retrieved, serum estradiol concentration and number of the available embryo were significantly higher in SERa + cycles than in SERa- cycles (P < 0.05). Comparable two pronuclei (2PN) fertilization rate and poly-pronucleus zygote rate were shown in SERa + and SERa- cycles (P > 0.05), but which were higher in SERa + oocytes than in SERa- oocytes (P < 0.05). No statistical difference in blastocyst formation rate was found in SERa + and SERa- cycles as well as in SERa + and SERa- oocytes (P > 0.05). Good-quality embryo rate was statistically higher in SERa- cycles than in SERa + cycles (P < 0.05), but the difference was comparable between SERa + and SERa- oocytes (P > 0.05). No statistical difference in clinical pregnancy rate, spontaneous abortion rate, live birth rate and premature delivery rate were found in SERa + and SERa- cycles as well as in SERa + and SERa- oocytes (P > 0.05). The implantation rate was comparable in SERa + and SERa- cycles (P > 0.05), but it is higher in the group of only SERa- embryo transfer when compared with the group of mixed SERa + and SERa- embryo transfer (P < 0.05). 159 newborns in SERa + cycles and 140 newborns in SERa- cycles were followed up. Comparable newborn malformation rate was observed between SERa + and SERa- cycles and oocytes (P > 0.05). Logistic regression analysis revealed number of oocytes and total dose of Gn were risk factors for SERa occurrence (aOR = 1.05 and 1.55, P < 0.001).ConclusionOocyte's SERa is correlated with a number of oocytes retrieved and higher Gn dose, but it does not affect pregnancy outcomes and increase newborn malformation rate.

Minimal Stimulation Using Gonadotropin-Releasing Hormone Antagonist is Associated with Higher Live Birth Rates: A National Study of 13,050 Cycles.

The optimal protocol for minimal stimulation in vitro fertilization (IVF) has yet to be established. This study aims to determine if the use of gonadotropin-releasing hormone (GnRH) antagonist during minimal stimulation improves outcomes. All cycles designated as minimal stimulation from 2014 to 2016 from the Society for Assisted Reproductive Technology Clinic Online Reporting System were identified. Cycles in which GnRH antagonist was administered (n = 5984) were compared to those that did not receive it (n = 7066). Wilcoxon's rank-sum test and chi-square test were used to analyze continuous and categorical variables. A total of 6750 patients undergoing 13,050 cycles were included. GnRH antagonist use was associated with a significantly higher total gonadotropin dosage (median 975.0 [interquartile range, IQR, 600.0, 1575.0] vs. median 660.0 [IQR 375.0, 975.0], p < 0.001), lower cycle cancelation rate (11.3% vs. 13.6%, p < 0.001; OR 1.24, 95% CI 1.12-1.38, p < 0.001), and higher live birth rate (4.3% vs. 2.1%, p < 0.001; OR 0.47, 95% CI 0.39-0.58, p < 0.001). GnRH antagonist use was associated with a significantly higher live birth rate in women ≥35 years of age (2.7% vs. 0.9%, p < 0.001; OR 0.34, 95% CI 0.25-0.47, p < 0.001) and antimullerian hormone <1 (4.9% vs. 2.6%, p = 0.004; OR 0.52, 95% CI 0.33-0.81, p = 0.004). The use of GnRH antagonist suppression during minimal stimulation IVF is associated with an improved live birth rate, especially in older women and in women with diminished ovarian reserve. Although GnRH antagonist use may increase costs, it significantly decreases cancelation rate, increases number of embryos cryopreserved, and should be encouraged for minimal stimulation IVF.

Serum Gonadotropin Levels Predict Post-Trigger Luteinizing Hormone Response in Antagonist Controlled Ovarian Hyperstimulation Cycles.

The objective of this study was to investigate the utility of using serum gonadotropin levels to predict optimal luteinizing hormone (LH) response to gonadotropin releasing hormone agonist (GnRHa) trigger. A retrospective cohort study was performed of all GnRH-antagonist controlled ovarian hyperstimulation (COH) cycles at an academic fertility center from 2017-2020. Cycles that utilized GnRHa alone or in combination with human chorionic gonadotropin (hCG) for trigger were included. Patient and cycle characteristics were collected from the electronic medical record. Optimal LH response was defined as a serum LH ≥ 40 mIU/mL on the morning after trigger. Total sample size was 3865 antagonist COH cycles, of which 91% had an optimal response to GnRHa trigger. Baseline FSH (B-FSH) and earliest in-cycle LH (EIC-LH) were significantly higher in those with optimal response. Multivariable logistic regression affirmed association of optimal response with EIC-LH, total gonadotropin dosage, age, BMI and Asian race. There was no difference in the number of oocytes retrieved (p = 0.14), maturity rate (p = 0.40) or fertilization rates (p = 0.49) based on LH response. There was no difference in LH response based on use of combination vs. GnRHa alone trigger (p = 0.21) or GnRHa trigger dose (p = 0.46). The EIC-LH was more predictive of LH trigger response than B-FSH (p < 0.005).The optimal B-FSH and EIC-LH values to yield an optimal LH response was ≥ 5.5 mIU/mL and ≥ 1.62 mIU/mL, respectively. In an era of personalized medicine, utilizing cycle and patient characteristics, such as early gonadotropin levels, may improve cycle outcomes and provide further individualized care.

Role of N-acetylcysteine treatment in women with advanced age undergoing IVF/ICSI cycles: A prospective study.

ObjectiveThe main objective of this study was to explore the efficacy of a new antioxidant N-acetylcysteine (NAC) supplementation in reproductive outcomes of advanced age women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET), and the effect on the expression of L-glutathione (GSH) in follicular fluid (FF) and mitochondrial DNA (mtDNA) copy number of granulosa cells.MethodsThe present prospective randomized controlled study was conducted in 200 patients with advanced age women undergoing GnRH antagonist protocol. The treatment group (group A) consisted of 100 women who received N-acetylcysteine treatment from the menstrual phase of the previous cycle for about 45 days using the GnRH antagonist protocol. The control group (group B) consisted of 100 women who received the same protocol without N-acetylcysteine. Total gonadotrophin dosage the number of oocyte received, high-quality blastocysts, and pregnancy outcomes were compared between two groups. Pregnancy outcomes included biochemical pregnancy rate, clinical pregnancy rate, embryo implantation rate, ectopic pregnancy rate, multiple pregnancy rate, and ongoing pregnancy rate. Follicular fluid (FF) was collected after oocytes were gathered. The GSH content in the FF was tested with enzyme linked immunosorbent assay (ELISA). The mtDNA copy number of the granulosa cells was measured using real-time PCR techniques.ResultsTotal doses of Gn in the NAC treatment group were less than those in the control group (2385.50 ± 879.19 vs. 2527.63 ± 1170.33, P = 0.047). Compared with the control, the number of high-quality blastocysts in NAC treatment increased significantly (1.82 ± 2.12 vs. 1.43 ± 1.58, p = 0.014). Clinical pregnancy rates did not differ in both groups (all P > 0.05). At the same time, the GSH content in the FF differed significantly between the two groups (1.88 ± 1.23 vs. 1.07 ± 0.70, p = 0.001). There was no significant difference in the mtDNA copy number between the two groups (P = 0.157).ConclusionA combination of NAC and Gn treatment is capable of improving the ovarian response to superovulation drugs in assisted reproductive technologies (ARTs) and also in aged populations. The addition of NAC during IVF can improve the quality of blastocysts in advanced age female subjects. However, more clinical trials are required to be designed to confirm this conclusion in future.Ethics and disseminationThe experiment solicited approval from the Institutional ethics committee of the Affiliated Reproductive Hospital of Shandong University. All the participants provided written informed consent. This survey was conducted as per the Declaration of Helsinki and relevant amendments.Trial registration numberwww.chictr.org.cn, identifier ChiCTR2100048297.

SELECTION OF OPTIMAL GONADOTROPIN DOSE USING MACHINE LEARNING MAY BE ASSOCIATED WITH IMPROVED OUTCOMES AND REDUCED UTILIZATION OF FSH

We previously developed a machine learning model for selecting an individualized gonadotropin dose for ovarian stimulation based on patient similarity matching [1]. The purpose of this study was to evaluate this methodology on a large and diverse dataset to retrospectively determine associations between machine learning predictions, patient outcomes, and total gonadotropin used.

Effect of weight loss on pregnancy outcomes, neuronal-reproductive-metabolic hormones and gene expression profiles in granulosa cells in obese infertile PCOS patients undergoing IVF-ET.

ObjectiveTo investigate the effect of weight loss on pregnancy outcomes, PCOS related neuronal-reproductive-metabolic hormones and ovarian granulosa cell gene expression profiles in obese PCOS infertile patients undergoing in vitro fertilization-embryo transfer (IVF-ET).Methods75 patients undergoing IVF-ET due to tubal factors alone collected as the control group (group A), and 352 patients with obese PCOS infertility were divided into four groups according to the amount of weight loss before IVF: 0 kg (group B), 1-5 kg (group C), 5-10 kg (group D), and >10 kg (group E). Six cases of ovarian granulosa cells were collected randomly with the random number table method in each group for detecting mRNA profiling. Pathway networks and biological functions of the differentially expressed genes were analyzed. Validation by RT-PCR was performed.Results(1) The levels of luteinizing hormone(LH), testosterone(T) and homeostasis model assessment insulin resistance(HOMA-IR) in group E were significantly lower than those in groups B and C (P<0.05). (2) Compared with groups A and E, groups B and C showed increased total gonadotropin (Gn) and days of Gn stimulation (P<0.05), and the E2 level on trigger day and number of oocytes obtained in group B was significantly less than that in group E (P<0.05 or 0.01). Embryo implantation rate, clinical pregnancy rate and live birth rate were increased and miscarriage rate was decreased in groups A, D and E compared with group B (P<0.05 or 0.01). (3) There were significant differences among the control group and PCOS groups in some genes that are involved in neuronal-reproductive-metabolic endocrine, transcriptional regulation, cell proliferation and differentiation, etc (P<0.05). RNA-Seq results were validated by real time PCR analysis for the expression of follicle stimulating hormone receptor (FSHR), drosophila mothers against decapentaplegic protein 7(Smad7) and glutathione peroxidase 3(GPX3) genes that are known to have an important role in follicular development. Functional alterations were confirmed by the improvement in the ovarian responsiveness to Gn and embryo quality.ConclusionWeight loss more than 5kg may regulate the neuroreproductive endocrine hormone secretion, insulin resistance and gene expression profiles of ovarian granulosa cells, so as to improve the ovarian responsiveness to Gn, the embryo quality, embryo implantation rate, clinical pregnancy rate, live birth rate, and reduce the spontaneous abortion rate in obese infertile PCOS patients undergoing IVF-ET.Clinical trial registration www.chictr.org.cn, identifier ChiCTR1800018298.

The effect of androgen administration on in vitro fertilization outcome in poor responders undergoing ovarian stimulation with microdose protocol: A randomized clinical trial

Objective(s)Patients with poor ovarian response who have reduced ovarian reserve sometimes despite the maximum dose of gonadotropins do not respond properly. Androgens have been shown to play an important role in the early follicular development and proliferation of granulosa cells. This study aimed to evaluate the effect of androgen administration on IVF outcome in poor responders. Study DesignIn this randomized clinical trial, 60 poor responder women candidate for controlled ovarian stimulation were randomly enrolled in two groups (n = 30/each). In the intervention group testosterone gel added to the interrupted microdose flare protocol. The control group received the conventional microdose flare protocol. ResultsThe main outcome was clinical and chemical pregnancy; and the second outcomes were the number of mature oocytes, duration of cycle and total dose of gonadotropins. Basic clinical and demographic features were comparable between the groups. The total gonadotropin consumption were significantly higher in the control group than the intervention group (p = 0.047). In addition, the number of MII oocytes was higher (but not significant) in the intervention group than the control group (p = 0.16). The mean total duration of the cycle was equal in both groups. There were no significant differences in chemical and clinical pregnancy rates between the two groups (p = 0.41, p = 0.67). Conclusion(s)The results of the current study showed that androgen administration in poor responders in in vitro fertilization reduces the total dose of gonadotropin, but it does not improve the pregnancy outcomes.

The Impact of Malignancy on Assisted Reproductive Outcomes for Cancer Survivors: A Retrospective Case-Control Study.

BackgroundRelated studies have shown that it is safe for cancer patients to undergo assisted reproduction. However, studies on whether a history of cancer affects long-term reproductive outcomes in women who undergo assisted reproductive technology (ART) are scarce. In this study, we evaluated the long-term reproductive outcomes of patients with malignant tumors undergoing ART treatment and explored the impact of malignancy history on ART outcomes.MethodsThis retrospective study analyzed the clinical outcomes of patients with malignant tumors undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles compared with those of age-matched healthy infertile women at Fujian Maternity and Child Health Hospital between January 2003 and October 2020. We evaluated ovarian stimulation outcome, the pregnancy rate, the live birth rate, the risk of adverse obstetric outcomes and birth outcomes.ResultsThis study included 59 patients in the cancer group for data analysis who had a history of malignancy. By matching, a total of 118 healthy infertile women were included in the control group. No statistically significant association was found in terms of age, duration of infertility, BMI, or insemination type between the two groups of patients. Thyroid cancer(45.8%) and gynecologic malignancies (44.07%) were the major cancer types in this study. There were statistically significant differences in the antral follicle count (AFC) (12.00 ± 7.86 vs. 14.90 ± 8.71, P=0.033), length of ovarian stimulation (9.98 ± 2.68 vs. 11.42 ± 2.43, P=0.033) and endometrial thickness on the trigger day (10.16 ± 3.11 vs. 10.84 ± 2.17, P<0.001) between the two groups. The total gonadotropin dose, number of oocytes retrieved, fertilization rate, cleavage rate, high-quality embryo rate, blastocyst rate and first-time embryo-transfer (ET) implantation rate were nonsignificantly lower in the cancer group than in the control group (P>0.05). There were no significant differences in the clinical pregnancy rate per ET cycle (32% vs. 40.39%, P=0.156), live birth rate per ET cycle (27% vs. 35.96%, P=0.119), miscarriage rate per ET cycle (5% vs. 4.43%, P=0.779), or preterm delivery rate per ET cycle (11.11% vs. 17.80%, P=0.547) between the two groups. Additionally, regression analysis showed that a history of malignancy was not a risk factor for reproductive outcomes.ConclusionsOverall, it is feasible for women with a history of cancer to conceive using ART is feasible and their long-term reproductive outcomes are similar to these of healthy infertile women. A history of cancer does not decrease the number of retrieved oocytes, increase the risk of adverse obstetric outcomes or affect birth outcomes.

Letrozole cotreatment with progestin-primed ovarian stimulation in women with polycystic ovary syndrome undergoing IVF treatment.

Background: Progestin is an alternative to gonadotropin-releasing hormone (GnRH) analogues in the follicular phase to suppress the premature luteinizing hormone (LH) surge in women with polycystic ovary syndrome (PCOS). However, progestin-primed ovarian stimulation (PPOS) is always accompanied by increased pituitary suppression and gonadotropin consumption. Previous studies suggested that letrozole appeared to have the potential to reduce the total gonadotropin dose required for ovarian stimulation. A retrospective cohort study was performed to evaluate the efficacy of PPOS with or without letrozole in infertile women with PCOS. Methods: This retrospective cohort study included 448 women with PCOS who underwent controlled ovarian stimulation (COS) with human menopausal gonadotropin (hMG) and medroxyprogesterone acetate (MPA) (n = 224) or hMG and MPA cotreatment with LE (n = 224) from January 2018 to March 2021 after propensity-score matching. The primary outcome measure was the hMG dose. The secondary outcomes were the durations of ovarian stimulation, the implantation rate, the number of oocytes retrieved and viable embryos, oocyte maturity and fertilization rates, the percentage of women with profound pituitary suppression (luteinizing hormone [LH] <1.0 IU/L on the trigger day). Results: The hMG doses (1949.89 ± 725.03 IU vs 2017.41 ± 653.32 IU, p > 0.05) and durations of ovarian stimulation (9.03 ± 1.79 days vs 9.21 ± 2.18 days, p > 0.05) were similar between the two groups. The implantation rate was significantly higher in the study group (MPA + hMG + LE) than in the control group (MPA + hMG) (42.22 vs 34.69%, p < 0.05). The numbers of oocytes and embryos retrieved were similar between the two groups. Interestingly, letrozole cotreatment was associated with decreased oocyte maturity and fertilization rates in comparison with standard PPOS protocols even though mature and fertilized oocyte yields were comparable. Compared with those in the control group, the LH values on the trigger day were significantly higher in the study group, together with significantly reduced pituitary suppression. Conclusion: Letrozole combined with PPOS cannot reduce hMG consumption in PCOS patients undergoing IVF treatment and shows no beneficial effect on cycle characteristics of COS. However, letrozole supplementation manifests as a superior implantation rate to that of the standard PPOS protocol in women with PCOS.

Clomiphene citrate priming increases sensitivity during ovarian stimulation in poor ovarian responders undergoing in vitro fertilization treatment: a retrospective cohort study

This single-centre retrospective cohort study aimed to investigate whether a clomiphene citrate (CC) priming protocol could increase ovarian sensitivity in poor ovarian responders. It included 294 patients (374 ovarian stimulation cycles). Of these, 193 cycles were treated by a CC priming antagonist protocol (study group) and 181 by the classical flexible gonadotropin-releasing hormone antagonist protocol (control group). Stimulation data and laboratory and clinical outcomes were compared between the groups. The results showed that in the study group, total gonadotropin dosage and dosage per follicle were considerably lower, the follicle-to-oocyte index was significantly higher, and the gonadotropin duration was shorter. After adjusting for potential confounders, multivariate regression analysis showed that cumulative ongoing pregnancy remained comparable between the groups (adjusted odds ratio: 0.761, 95% confidence interval: 0.300–1.933, p = 0.566). Age, body mass index, gonadotropin dosage per follicle, and the follicle-to-oocyte index were negatively associated with the reproductive outcomes. The result of the sensitivity analysis showed that patients in the study group were administered less gonadotropin at a lower gonadotropin dosage per follicle and for a shorter duration. In conclusion, the CC priming antagonist protocol offered a convenient and patient-friendly way to increase ovarian sensitivity during ovarian stimulation in poor ovarian responders.

Comparison of two ovarian stimulation protocols among women with poor response: A randomized clinical trial.

This is a randomized controlled trial conducted in a tertiary referral fertility department. Participants were women with previous poor ovarian response undergoing in vitro fertilization. (IVF). One hundred and ninety-two women were randomized to the short GnRH agonist and antagonist regimens. The primary outcome was the number of oocytes retrieved. Secondary outcome measures were the number of embryos transferred, chemical and clinical pregnancy rate and live birth. The number of oocytes retrieved was higher with the gonadotrophin-releasing hormone (GnRH) antagonist regimen compared to the short agonist regimen (3.10 2.70 vs. 2.992.60), but there was no significant difference. The duration of stimulation and total gonadotropin dose were higher with short agonist regimens compared to antagonist regimens, with the latter being statistically significant (p < 0.001). The chemical pregnancy rate was 8.33 percent with the short agonist regimen and 7.29 percent with the antagonist regimen, with no statistically significant difference (p = 0.79). In terms of lower cycles cancelation and higher chemical pregnancy, short GnRH agonist regim is appropriate choice for poor responders.

PLACENTA-ASSOCIATED PLASMA PROTEIN AND FREE HUMAN CHORIONIC GONADOTROPIN LEVELS IN DAY 3 VERSUS DAY 5 TRANSFER

Aim: This study was conducted to investigate placenta-associated plasma protein (PAPP-A) and free human chorionic gonadotropin (B-hCG) levels after blastocyst transfer versus cleavage-stage embryo transfer. &#x0D; Materials and method: A total of 449 women were included in this rerospective sudy. The study consisted of two groups: Group 1: pregnant women conceived by intracytoplasmic sperm injection (ICSI) procedures after fresh embryo transfer at the cleavage stage (day 2 or day 3) and had first trimester fetal aneuploidy biochemical markers performed at 11-14th gestational week (n: 275). Group 2: pregnant women conceived by ICSI procedures after fresh embryo transfer at the blastocyst stage (day 5) and had first trimester fetal aneuploidy biochemical markers performed at 11-14th gestational week (n:174). Demographic characteristics, causes of infertility, duration of infertility, stimulation protocol regimens, total gonadotropin doses, number of follicles and oocytes retrieval, endometrial thickness, fundus –embryo distance were recorded and placenta-associated plasma protein (PAPP-A) and free human chorionic gonadotropin (B-hCG) levels were measured. &#x0D; Results: We found no significant differences in PAPP-A and free B-hCG levels, stimulation protocols regimens and endometrial thickness and fundus-embryo distance. Diminished ovarian reserve and total gonadotropin doses were significiantly higher in group 1 (p &lt; 0.05). Number of follicles, number of oocytes retrieval and MII oocytes were significiantly higher in group 2 (p &lt; 0.05). &#x0D; Conclusion: No difference was observed in PAPP-A and free B-hCG levels between the 3rd and the 5th day fresh transfer.

P-584 Dual trigger with hCG plus GnRHa for final oocyte maturation in PGT-A cycles results in similar euploidy rates when compared to hCG only trigger

Abstract Study question To assess whether dual trigger alters the ploidy chance of a blastocyst in preimplantation genetic screening for aneuploidy (PGT-A) cycles Summary answer Compared to hCG triggerring, dual triggerring does not provide an additional superiority on blastocyst euploidy rate. What is known already Variables that may affect euploidy rates in various stages of an IVF cycle such as total gonadotropin dosage, stimulation regimen, ovarian response and switching to natural cycle were not shown to affect blastocyst euploidy rates. Furthermore, there is no difference when final oocyte maturation is triggered with hCG or GnRHa. On the other hand, it has been shown that dual trigger with hCG plus GnRHa may result in a higher maturation rate in oocytes, compared to hCG only trigger. There are controversial data in the literature about the effect of dual trigger on euploidy rates. Study design, size, duration This is a retrospective cohort study of 385 PGT-A cycles performed over a 7-year time period between May 2012 and April 2019 at a single tertiary center for various indications. Participants/materials, setting, methods All couples undergoing IVF/intracytoplasmic sperm injection (ICSI) with planned PGT-A were included in the study, regardless of whether an embryo transfer was performed or not. Final oocyte maturation was triggerred using human chorionic gonadotropin (hCG) or the combination of hCG and gonadotropin releasing hormone agonists (GnRHa) (Dual trigger). Participants were divided based on triggering method and all demographic and clinical characteristics of the patients were compared. Main results and the role of chance Final oocyte maturation was triggered in 143 cycles with hCG (37.1 %), and in 242 cycles with dual trigger (62.9 %). The duration of stimulation was shorter in dual trigger arm compared to hCG trigger group (10.0 ± 1.6 vs. 9.4 ± 1.4 days, p = &amp;lt;.001). Euploidy rates per blastocyst tested were 23.4 %, and 26.1 % respectively for hCG and dual trigger groups with no significant difference. When the patients were stratified according to age, euploidy rate was higher in the dual trigger group in all age groups with no significance. There was no significant difference between hCG and dual trigger groups, regarding positive pregnancy result and ongoing pregnancy rates (p = .779 vs. p = .188). Limitations, reasons for caution Retrospective design and small sample size could be accepted as the limitations. Wider implications of the findings Our study is the first study in literature exploring the ploidy status of embryos following dual trigger with hCG + GnRHa for final oocyte maturation in PGT-A cycles and, comparing it with hCG only trigger. Dual triggerring of final oocyte maturation results in similar euploidy rates in blastocysts tested. Trial registration number 2020/004

P-673 GnRH Agonist Early Follicular Challenge Test as a Predictor of Ovarian Response in Short Antagonist Cycles for Fertility Preservation

Abstract Study question Does the response to GnRH agonist can be used to predict ovarian function in short GnRH antagonist cycles in women undergoing oocyte cryopreservation IVF cycles? Summary answer Response to a single GnRH agonist dose at the beginning of stimulation during short antagonist cycle can predict the outcome of the fertility preservation cycle What is known already There is a need for a reliable test for ovarian reserve. Gonadotrophin agonist stimulation test (GAST) is considered a valid marker for ovarian reserve but the test was never validated for short antagonist protocol. The reported dose for this test was 0.1 mg, however, from the vast experience with GnRH agonist triggering, it is now agreed that the optimal dose for GnRH agonist flare effect is 0.2 mg. Study design, size, duration A prospective observational study of fertility preservation cycles patient in an academic hospital setting. Seventy-four Short GnRH antagonist cycles that underwent an oocyte retrieval between 1 December 2020 and 1 January 2022. Participants/materials, setting, methods On day 2, blood was sampled for basal FSH, LH, and E2 measurements, followed by a subcutaneous injection of 0.2mg GnRH agonist as part of the initial ovarian stimulation. Twelve hours later blood sampling was repeated. E2 response was used as test parameter. The major outcome was the number of cryopreserved oocytes. Main results and the role of chance Participants were divided to groups according to Day 3 E2 to Day 2 E2 response (E3/E2 ratio) to lower and upper third percentiles (&amp;lt;3.32, n = 24 and &amp;gt;5.41, n = 25). Age (32.68 vs. 32.79, p = 0.965), total gonadotropin dose injected 3216.67 vs. 2773.42 IU p = 0.16) and day 3 FSH levels (7.39 vs. 7.16, p = 0.768) were not significantly different between groups. Ovarian response as measured by E2 levels on ovulation trigger (7879.72 vs. 17572.54 pmol/ml, p = 0.001) and number of M2 oocytes retrieved were significantly different (17.92 vs. 6.24, p &amp;lt; 0.001). Linear correlation between E3/E2 ratio and number of M2 oocytes was calculated (R = 0.48, p &amp;lt; 0.001). ROC curve analysis of E3/E2 ratio for more than fifteen M2 oocytes indicate AUC value of 0.82 (cutoff value of 4.22, p &amp;lt; 0.001, 84.6% sensitivity, 70.8% specificity) and for less than five M2 oocytes AUC value of 0.84 (cutoff value of 3.34, p &amp;lt; 0.001, 76.3% sensitivity, 73.3% specificity). The results suggest that the testing response to 0.2mg GnRH agonist positively correlates with treatment outcome of the current cycle. Limitations, reasons for caution Although all patients were tested for FSH levels for ovarian reserve, they were not tested for AMH levels. Wider implications of the findings The response to single GnRH agonist dose during short antagonist cycle can be used as another biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict accurately the outcome of the specific cycle, and potentially used to adjust the treatment dose. Trial registration number NCT04973969

P-465 A systematic review and meta-analysis of ovarian stimulation outcomes in cancer patients opting for oocyte cryopreservation prior to treatment compared to social egg-freezers

Abstract Study question Do patients with malignancy undertaking oocyte cryopreservation (OC) prior to cancer treatment have comparable cycle outcomes to patients having OC for social reasons? Summary answer Cancer patients achieve similar oocyte yields following ovarian stimulation to social freezers. However, they express lower peak oestradiol (E2), antral follicle count(AFC), and anti-Mullerian hormone(AMH). What is known already Increasing numbers of women are diagnosed with cancer in their reproductive years. Medical advances have led to earlier detection, improved treatments, and higher survival rates. However, cytotoxic cancer therapy is known to have a negative impact on ovarian reserve and fertility. Oocyte cryopreservation prior to such treatments provides a means of preserving fertility. Statistics on cycle outcomes often comes from social egg-freezers, however it is not yet known if patients with malignancy opting to preserve oocytes prior to treatment can expect the same results as their healthy counterparts. Study design, size, duration A literature search was performed on databases MEDLINE, EMBASE and Web of Science. Relevant text words and MeSH headings were used to identify all relevant papers. Studies reporting cycle outcomes of either oncology patients or social egg-freezers, or compared both were included. Only manuscripts that reported the number of mature oocytes obtained through controlled ovarian stimulation were included. Participants/materials, setting, methods All patients presenting for oocyte cryopreservation prior to cancer therapy were included with no distinction made between cancer type. Controls included women presenting for oocyte cryopreservation for social reasons. Those presenting for male-factor infertility were not included. Data extracted included patient age total number of oocytes retrieved, peak E2, AFC, AMH, gonadotropin dose, and days of stimulation. Statistical heterogeneity was calculated and outcomes were presented to a 95% confidence interval (CI). Main results and the role of chance A search of the databases retrieved 3805 articles, 116 of which remained for full-text evaluation after duplicates were removed and article titles and abstracts were assessed. Twenty-two articles met the inclusion criteria and were included in the meta-analyses. Total number of oocytes retrieved was similar between both groups with no significant difference in the means [standard mean difference mean difference (SMD) 1.069, 95% CI -1.1169 to 3.2549]. Peak E2, AFC, and AMH were all significantly lower in cancer patients with a SMD of -1031.4 (95% CI -1805.2 to -257.7), 0.277 (95% CI 0.042 to 0.511), and -2.289 (95% CI -3,913 to -0.665) respectively. There was no significant difference observed in number of mature (M2) oocytes, total gonadotropin dose or number of stimulation days with an SMD of -0.022 (95% CI -1.861 to 1.817), 188.75 (95% CI- 432.86 to 810.35), and 0.002 (95% CI -0.439 to 0.443) respectively. Limitations, reasons for caution Population characteristics, age, and BMI (major factors in fertility prognostics) were inconsistent between studies. Differences in cancer type, stage, grade, and stimulation protocols also potentially contributed to high heterogeneity. Few studies report obstetric outcomes, which could not be evaluated. Live-birth rate has arguably greater clinical significance but requires improved reporting. Wider implications of the findings This research supports the view that cancer negatively impacts ovarian reserve and supports an argument for improved patient access to fertility preservation. As clinical practice improves cancer survivor rates, a responsibility lies with healthcare professionals to provide evidence-based and accurate counselling for patients to make informed decisions about their fertility. Trial registration number Not applicable

P-609 Comparison of fixed and flexible progestin primed ovarian stimulation protocols to prevent luteinizing hormone surge in poor ovarian response

Abstract Study question Are fixed and flexible progestin primed ovarian stimulation (PPOS) protocols comparable in preventing luteinizing hormone (LH) surge in poor response group? Summary answer Both PPOS protocols are comparable in preventing LH surge in poor response group. Fertilization and clinical pregnancy rates are also similar. What is known already PPOS protocols are recently used as an alternative to gonadotropin releasing hormone (GnRH) antagonists for pituitary suppression. Oral administration and lower costs of progestins are advantageous, while fresh embryo transfer is precluded due to high progesterone exposure and impaired endometrial receptivity. However, PPOS protocol is shown to be effective at planned all-freeze cycles in different patient populations. Recently progestins are also shown to prevent LH surge when administered in later phase of the cycle. Namely, flexible protocols are based on the follicle size or hormone values. Few studies compared flexible PPOS protocols with GnRH antagonist protocols, and declared similar outcomes. Study design, size, duration This retrospective cohort study was conducted in a single center, including the PPOS cycles of poor response patients in 3 years period, between January 2019 and December 2021. Participants/materials, setting, methods A hundred sixteen poor ovarian response patients who were administered PPOS protocols for pituitary suppression were included. Eighty-six patients received fixed protocol, where 20 mg/day dydrogesterone was started in cycle day 3 along with gonadotropins and continued until trigger day, while thirty patients received flexible protocol, where 20 mg/day dydrogesterone was started when the leading follicle reached 14 mm or in stimulation day 6. Descriptive features and cycle characteristics of the two groups were evaluated. Main results and the role of chance Indications for PPOS protocol included diminished ovarian reserve and poor ovarian response. Baseline characteristics including age, antral follicle count, anti mullerian hormone levels, and infertility period were similar in both groups (p &amp;gt; 0.05), while body mass index was higher in the flexible protocol group (median values were 23.3(16.8-35.9) and 26.6(19.4-35.8) kg/m2, in fixed and flexible groups respectively, p = 0.004). Cycle parameters including total days of gonadotropin administration, total gonadotropin dose, progesterone and estradiol values and endometrial thickness at trigger day were similar (p &amp;gt; 0.05). Retrieved oocytes numbers and metaphase II oocyte numbers were higher in the fixed protocol group, however 2PN numbers were similar (p = 0.030, 0.013 and 0.079, respectively). LH surge, which was demonstrated by progesterone value higher than 1.2 ng/mL on trigger day, occured at 5.8% and 6.7% patients in fixed and flexible PPOS protocols, respectively (p = 1.000). Clinical pregnancy rates were 64.1% in fixed protocol and 42.9% in flexible protocol groups, which were also statistically similar (p = 0.407). Limitations, reasons for caution Retrospective nature and small number of patients together with unbalanced numbers of cases in the two groups are the limitations of the study. Wider implications of the findings Flexible PPOS protocol has been studied recently, and necessitate further prospective research. It seems to be a patient friendly stimulation protocol, however, studies, particularly on certain subgroups such as diminished ovarian reserve should be conducted to elucidate its effectiveness. Trial registration number not applicable

O-130 Reproductive outcomes of normal ovarian reserve patients after progestin-primed ovarian stimulation with chlormadinone acetate vs GnRH antagonist: A retrospective study with inverse-probability-of-treatment weighting

Abstract Study question To evaluate the effectiveness of chlormadinone acetate (CMA) for preventing premature LH surge in patients with normal ovarian reserve compared to cetrorelix. Summary answer In progestin-primed ovarian stimulation (PPOS) than GnRH antagonist (GnRH-ant), the incidence of premature LH surge was significantly lower, without significant difference in oocyte maturation rate. What is known already The GnRH-ant protocol is one of the conventional protocols which has some disadvantages including increased premature LH surge rate and cancelation rate. In recent years, the PPOS protocol has attracted attention as a new ovarian stimulation using progestin as an alternative to GnRH analog for suppressing a premature LH surge, however its efficacy is still controversial. In addition, many studies have investigated the reproductive outcomes of PPOS using medroxy-progesterone acetate or dydrogesterone; however, there are few reports of CMA, an oral progestin, which is inexpensive and widely used in Japan. Study design, size, duration This retrospective cohort study was performed in a reproduction center between March 2018 and October 2020 which included 977 Japanese patients with normal ovarian reserve undergoing PPOS with CMA (n = 299), or GnRH antagonist (GnRH-ant) with cetrorelix (n = 608) in their first IVF cycle at the reproduction center. In subgroup analysis, pregnancy outcomes after frozen embryo transfers (FET) between PPOS (n = 284) and GnRH-ant (n = 579) were also compared. Participants/materials, setting, methods The inclusion criteria were patients aged &amp;lt; 40 years and AMH ≧ 1.1 ng/mL, who underwent autologous oocyte retrieval in their first IVF cycle with freeze-all strategy. The primary outcome was the incidence of premature LH surge, the secondary outcomes was oocyte maturation rate. To reduce the impact of treatment bias and potential confounding factors, we conducted logistic regression models with inverse-probability-of-treatment weighting (IPTW). Main results and the role of chance After IPTW, baseline clinical data were well-balanced between the two groups, including age, AMH, BMI, the duration, type, and cause of infertility, antral follicle count, the history of recurrent spontaneous abortion, and previous IVF attempts. The premature LH surge rate was significantly lower with PPOS (3.1%) compared to GnRH-ant (20.1%) (odds ratio, 0.21; 95% confidence interval, 0.11–0.36). No significant differences were found in total gonadotropin dose (2400IU for PPOS vs 2400IU for GnRH-ant, p = 0.136), the number of oocyte retrieval (n = 15 vs n = 15, p = 0.484), oocyte maturation rate (78.8% vs 77.8%, p = 0.275), fertilization rate (73.0% vs 72.0%, p = 0.412), viable embryo rate per oocyte retrieval (40% vs 40%, p = 0.890), and good quality blastocyst rate (72.0% vs 69.6%, p = 0.092). However, the good quality day-3 embryo rate was significantly lower with PPOS (37.2% vs 49.1%, p &amp;lt; 0.05). There were no differences in the incidence of moderate-to-severe OHSS (0.3% vs 0.7%, p = 0.481). In FET cycles, the pregnancy outcomes, such as implantation rate (43.1 % vs 51.9 %, p = 0.013) and clinical pregnancy rate (46.5% vs 54.7%, p = 0.027) were significantly lower with PPOS, however, no significant differences were found in ongoing pregnancy rate (75.6% vs 80.5%, p = 0.325), and live birth rate (72.4% vs 79.5 %, p = 0.142). Limitations, reasons for caution This was a retrospective cohort study conducted in a single center. The participants in this study were limited to Japanese ethnicity. The results need to be validated across different centers and other ethnicities. Wider implications of the findings This is the first report assessing the reproductive outcomes on PPOS using CMA, widely used in Japan. The PPOS with CMA significantly suppressed the premature LH surge rate compared to GnRH-ant protocol, without decrease in oocyte maturation rate. Trial registration number N/A

P-694 Dosage of exogenous gonadotropins is not related to blastocyst aneuploidy or cumulative live-birth rates in PGT-A cycles

Abstract Study question Does dosage of gonadotropins affect aneuploidy rate rates or cumulative live birth rates (CLBRs) after the transfer of euploid embryos? Summary answer We did not find evidence that dosage gonadotropin influenced significantly the rate of aneuploidy and CLBRs after transfer of euploid embryos. What is known already Aneuploidy rates increase steadily with age, reaching &amp;gt;80% in women &amp;gt;42 years old. The goal of controlled ovarian stimulation obtaining more embryos to biopsy through the recruitment of several follicles, reaching more euploid embryos. However, several studies have suggested that a high response to stimulation might be embryotoxic and/or increase aneuploidy rates by enhancing the abnormal segregation of chromosomes during meiosis. Furthermore, a study on young donors showed differences in the euploidy rates, suggesting an iatrogenic etiology resulting from different stimulation methods. Study design, size, duration A multicenter retrospective study, with the preimplantation genetic test for aneuploidy (PGT-A) between January 2013 and January 2020 collected from clinics IVIRMA in Europe. 6832 cycles of in vitro fertilization (IVF) with PGT-A were included in the study Participants/materials, setting, methods A total of 62131 embryos were analyzed for ploidy status. Embryos that were subjected to chromosomal analysis were performed blastomere by aCGH (array Comparative Genomic Hybridization) or NGS (Next-Generation Sequencing) analysis. The embryos were biopsied on days 5 and 6. Women were divided into two age groups (&amp;lt;37 and ≥37 years old). Outcomes were compared between different total gonadotropin dosages (&amp;lt;3000 and ≥3000 IU), the dosage of hMG, and numbers of oocytes retrieved. Main results and the role of chance The total number of aneuploid embryos was 28336 of the 62131 embryos genetically screened using PGT-A. The embryonic aneuploidy rate was 59.4% (95%CI 58.5-60.3). In the group of women with gonadotropins dosage &amp;lt;3000 IU the embryonic aneuploidy rate was 59.7% (95%CI 58.7-60.8) and in the group with gonadotropins dosage ≥3000 IU was 58.7% (95%CI 57.1-60.3) with no significant difference between them (P = 0.279). In the group of younger patients (&amp;lt;37 y.o) the aneuploidy rate demonstrated no significant differences between patients who received low gonadotropin dosages and patients with high gonadotropin dosages (P = 0.06). Aneuploidy rates in the group of older patients (≥37 y.o) were similar regardless of gonadotropin dosing (P = 0.21). Dividing the according to the number of oocytes retrieved (10, 11-15, &amp;gt;15), the analysis of aneuploidy rate revealed no association between the gonadotropin dosages administrated depending on the total number of retrieved oocytes and age. The aneuploidy rate was also analyzed considering the administration of hMG, there was no statistical difference in the aneuploidy rate with low or high hMG dosages also when it was stratified by age. The cumulative live-birth rate in the groups of different gonadotropins dosage and different ages of patients was similar across the group. Limitations, reasons for caution The retrospective nature is the major limitation of this study, also patients included in the study received PGT-A using NGS and CGH arrays technology. The aCGH analysis used is less sensitive than more recent NGS technology. Wider implications of the findings Our study demonstrated that gonadotropin dosage did not affect aneuploidy rate or cumulative live-birth rates suggesting that the high doses of gonadotropins used in ART cycles may be safe. Trial registration number not applicable