Human Menopausal Gonadotropin Research Articles

Resistant ovary syndrome: Two case reports and a literature review of effective controlled ovarian stimulation in IVF.

Resistant ovary syndrome (ROS) represents a rare reproductive endocrine disorder that is predominantly associated with infertility, characterized by heightened endogenous gonadotropin levels in the presence of a normal ovarian reserve. Patients with ROS typically exhibit a poor response to exogenous gonadotropins during controlled ovarian stimulation (COS). Due to the absence of a universally accepted effective COS protocol, this study aims to contribute to the existing body of literature by detailing 2 successful pregnancies achieved through conventional in vitro fertilization (c-IVF) in patients with ROS, and through retrospective analysis, seeks to elucidate the factors contributing to the successful ovarian stimulation in these cases, with the ultimate goal of establishing clinical guidelines for ROS management. The central challenge addressed in this study pertains to the effective induction of oocyte maturation during c-IVF COS in ROS patients. The study focuses on 2 infertile women diagnosed with ROS who sought to conceive via c-IVF. The patients were subjected to a COS protocol involving pituitary downregulation followed by ovarian stimulation using recombinant follicle-stimulating hormone (r-FSH) and human menopausal gonadotropin (HMG), preceded by 3 cycles of hormone replacement therapy (HRT) pretreatment. The proposed protocol elicited a favorable ovarian response, culminating in the retrieval of numerous mature oocytes and the development of multiple viable embryos via c-IVF, ultimately leading to successful live births post-embryo transfer. Our study suggests that the outlined COS protocol may serve as a viable treatment option for ROS patients aspiring to conceive through c-IVF, thereby potentially expanding the therapeutic repertoire for this challenging condition.

The allostery and modification of hGHRH molecules and specific dimer produced significant fertility effect by proliferating and activating in-situ ovarian mesenchymal stem cells

The negative coordination of growth hormone secretagogue receptor (GHS-R) and growth hormone-releasing hormone receptor (GHRH-R) involves in the repair processes of cellular injury. The allosteric U- or H-like modified GHRH dimer Grinodin and 2Y were comparatively evaluated in normal Kunming mice and hamster infertility models induced by CPA treatment. 1–3–9 µg of Grinodin or 2Y per hamster stem-cell-exhaustion model was subcutaneously administered once a week, respectively inducing 75–69–46 or 45–13–50 % of birth rates. In comparison, the similar mole of human menopausal gonadotropin (hMG) or human growth hormone (hGH) was administered once a day but caused just 25 or 20 % of birth rates. Grinodin induced more big ovarian follicles and corpora lutea than 2Y, hMG, hGH. The hMG-treated group was observed many distorted interstitial cells and more connective tissues and the hGH-treated group had few ovarian follicles. 2Y had a plasma lifetime of 21 days and higher GH release in mice, inducing lower birth rate and stronger individual specificity in reproduction as well as only promoting the proliferation of mesenchymal-stem-cells (MSCs) in the models. In comparison, Grinodin had a plasma lifetime of 30 days and much lower GH release in mice. It significantly promoted the proliferation and activation of ovarian MSCs together with the development of follicles in the models by increasing Ki67 and GHS-R expressions, and decreasing GHRH-R expression in a dose-dependent manner. However, the high GH and excessive estrogen levels in the models showed a dose-dependent reduction in fertility. Therefore, unlike 2Y, the low dose of Grinodin specifically shows low GHS-R and high GHRH-R expressions thus evades GH and estrogen release and improves functions of organs, resulting in an increase of fertility.

Experience in using biosimilars in IVF programs with donor oocytes in protocols with micronized progesterone

Relevance: Stimulation of oocyte donors' superovulation occupies a key place in the development of general assisted reproduction technology (ART). Oocyte donation programs involve young and healthy women undergoing severe ovarian stimulation protocols to obtain good-quality oocytes. Advances in recombinant DNA technology led to the development of recombinant follitropin alfa.The study aimed to evaluate the effectiveness of the biosimilar folitropin alfa in the superovulation stimulation cycles of oocyte donors in comparison with the original medication in Progestin primed ovarian stimulation (PPOS) protocols.Materials and Methods: A prospective cohort study included 25 oocyte donors who underwent superovulation induction. The first group consisted of 25 oocyte donors in whom superovulation was stimulated with a bio-analogue of follitropin alfa. The second group (control) included the same 25 oocyte donors stimulated with the original rFSH medication. The donors of the leading group were stimulated with biosimilar recombinant follicle-stimulating hormone and human menopausal gonadotropin. For the control group, a protocol was used using the original drug rFSH and CHMG in the same doses. The obtained donor oocytes were fertilized with ICSI or frozen. The program's result was determined by taking a blood test for b-hCG 14 days after embryo transfer.Results: The number of mature oocytes in the study groups did not differ significantly, amounting to 20.6 ± 1.1 in group 1 and 21.2 ± 1.3 in group 2. The average number of fertilized oocytes in group 1 was 5.6 ± 0.8, and in group 2 – 6.1 ± 1.1; thus, the fertilization rate in the two groups did not differ (67,5% in group 1 vs 79,2% in group 2, р> 0,05). The blastulation rate (49.1% in group 1 and 52.2% in group 2) did not differ significantly in both the biosimilar group and the original medication. The Top Quality Blastocysts in Group 1 were 1.5 ± 0.7 (55%) vs 1.8 ± 0.5 (48%) in Group 2. At the same time, the level of NNB in both groups also had no statistically significant differences.Conclusion: Sinnal-F was not inferior to the original medication in terms of the proportion of mature oocytes in oocyte donors. The study's results confirm that Synnal-f demonstrates favorable and comparable efficacy to the original medication in oocyte maturation in IVF/ICSI cycles.

The effect of human menopausal gonadotropin and equine chorionic gonadotropin on the reproductive performance of treated ewes with short-term progesterone injections and sponge during the non-breeding season.

This study investigated the effect of human menopausal gonadotropin (hMG) on reproductive efficiency of synchronized ewes with the sponge and progesterone (P4) injection-based protocols. In study 1, anoestrous ewes (n = 120) were used. Sixty ewes were treated with sponge (S) for 12 days. The injection of eCG (SeCG group, n = 30) or hMG (ShMG, n = 30) was given at the time of sponge removal. Thirty ewes received IM injection of P4, three times every 48 h and the injection of hMG was given 24 h after the third P4 injection (3PhMG group, n = 30), and 30 ewes were used as control group. Pregnancy was diagnosed on day 50 after the release of ram. In study 2, 60 ewes were randomly divided into two equal groups. In the treated group with antibiotics (n = 30), before inserting, the sponges were impregnated with the antibiotic penicillin G sodium (5,000,000 IU) and in the control group (n = 30), there was no added antibiotics. Before inserting and after removing sponges, a vaginal cytology sample was taken with a sterile cotton swab. The number of neutrophils in each sample was counted and analysed. The rate of oestrus and total pregnancy was greater in SeCG (96.7, 93.3%), ShMG (82.8, 93.1%) and 3PhMG (67.9, 89.3%) groups compared with the control group (13.8, 41.4%) (p < .05). No significant difference was found in single, twin and total lambing and pregnancy rates after injection of eCG and hMG during the non-breeding season (p > .05). A higher percentage of control ewes had the vaginal smear with neutrophils more than 50% (96.7% vs. 76.7%; p < .05). In conclusion, a single dose of hMG can induce fertile oestrus in synchronized ewes with P4 administered by either injection or intravaginally. Purulent discharge and percentage of neutrophils were significantly reduced in the synchronized ewes by the impregnated sponges with the antibiotic penicillin.

Effects of different gonadotropin preparations in GnRH antagonist protocol for patients with polycystic ovary syndrome during IVF/ICSI: a retrospective cohort study.

To compare the effects of recombinant FSH alfa (rFSH-alfa), rFSH-beta, highly purified human menopausal gonadotropin (HP-hMG) and urinary FSH (uFSH) in women with polycystic ovarian syndrome who have undertaken the GnRH antagonist protocol during IVF/ICSI treatment. A single-center retrospective cohort study including women with PCOS who received the GnRH antagonist protocol from January 2019 to July 2022 was conducted. Patients were divided into rFSH-alfa group, HP-hMG group, uFSH group, and rFSH-beta group, and the number of oocytes retrieved, clinical pregnancy rate of the fresh cycle (primary outcomes), embryo quality, and severe OHSS rate (secondary outcomes) were compared. No statistical differences were found among the four groups in fresh cycle clinical pregnancy rate (p=0.426), nor in the subgroup analyses. The HP-hMG group had a smaller number of oocytes retrieved and a higher high-quality D3 embryo rate than the three FSH groups (p<0.05). No statistical differences were found among the four groups in the severe OHSS rate (p=0.083). For women with PCOS undergoing the GnRH antagonist protocol, the clinical pregnancy rates of fresh IVF/ICSI-ET cycle are similar for all four types of Gn. With a lower risk of OHSS and a similar number of high-quality and available embryos, HP-hMG may have an advantage in the PCOS population.

P-48 Post-traumatic Panhypopitutarism after an in-vehicle traffic accident: A case report

Abstract Introduction Hypopituitarism, occurs most commonly from pituitary tumors and a head injury, though a fracture of the base of the skull is considered a rare cause. Traumatic brain injury causes severe disability and endocrine dysfunction in a significant proportion of patients. Hypopituitarism diagnosed with endocrine symptoms related to hypoadrenocorticotropinemia, hypothyroidism and hypogonadism. We describe a case of posttraumatic panhypopitutarism presenting with symptoms of secondary amenorrhea, loss of appetite, nausea, vomiting, hearing loss and hypoglycemia after an in-vehicle traffic accident. Clinical Case A 28-year-old female patient with no medical history was admitted with symptoms of nausea, vomiting, anorexia, amenorrhea, and hypoglycemia after an in-vehicle traffic accident. It was learned that the patient's menstrual periods were regular before the accident and she did not have any complaints. Panhypopitutarism was observed in the examinations performed (Table 1). In the follow-ups, 10% intravenous dextrose solution and 20 mg prednisolone every 6 hours were started due to the hypoglycemic course. Prednisolone was reduced and discontinued, and hydrocortisone treatment was started from 30 mg/day. L-thyroxine replacement was started one week after the steroid treatment. Computed tomography (CT) showed deformity and collapse secondary to the fracture at the base of the sella and on contrast-enhanced pituitary magnetic resonance (MRI) imaging, it was observed that the morphology of the sella was distorted in T1-weighted sections, pituitary tissue could not be clearly distinguished, and there was collapse at the base of the sella in the right lateral section; the present findings were thought to support pituitary insufficiency (Figure 1). Hormone replacement therapy was given for secondary amenorrhea. One year after the accident, she wanted to be a pregnant and ovulation was induced by the injection of human menopausal gonadotrophin (HMG) following human chorionic gonadotrophin (HCG) at a large dose. She got pregnant in the first cycle. Conclusion In a patient with Panhypopituitarism, who could not be pregnant spontaneously, clinical practice of ovulation–induction treatment including administration of hCG and follicle-stimulating hormone, pulsatile GnRH (gonadotropin-releasing hormone), and in vitro fertilization, enabled the hypopituitary women to become ovulation and pregnancy. In our case, pregnancy was achieved after adequate hormone replacement therapy.Figure 1.CT and MRI images of the patientFigure. (a) Coronal CT section showing deformity-subsidence at the base of the sella secondary to fracture, (b and c) sagittal and coronal contrast-enhanced MRI showing subsidence at the base of the sella (thick arrow) with herniation of pituitary tissue (short arrow) and distorted-deformed infundibular stalk (thin arrow), respectively. Table 1.Laboratory workup*ACTH: Adrenocorticotropic hormone; FSH: follicle-stimulating hormone; LH: Luteinizing hormone; TSH: thyroid stimulating hormone; fT4: thyroxine; GH: Growth hormone; IGF-1: Insulin-like growth factor 1

Gonadotropins for pubertal induction in males with hypogonadotropic hypogonadism: systematic review and meta-analysis.

Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical treatment with testosterone promotes virilization but not testicular growth or spermatogenesis. To quantify treatment practices and efficacy, we systematically reviewed all studies investigating gonadotropins for the achievement of pubertal outcomes in males with hypogonadotropic hypogonadism. Systematic review and meta-analysis. A systematic review of Medline, Embase, Global Health, and PsycINFO databases in December 2022. Risk of Bias 2.0/Risk Of Bias In Non-randomized Studies of Interventions/National Heart, Lung, and Blood Institute tools for quality appraisal. Protocol registered on PROSPERO (CRD42022381713). After screening 3925 abstracts, 103 studies were identified including 5328 patients from 21 countries. The average age of participants was <25 years in 45.6% (n = 47) of studies. Studies utilized human chorionic gonadotropin (hCG) (n = 93, 90.3% of studies), human menopausal gonadotropin (n = 42, 40.8%), follicle-stimulating hormone (FSH) (n = 37, 35.9%), and gonadotropin-releasing hormone (28.2% n = 29). The median reported duration of treatment/follow-up was 18 months (interquartile range 10.5-24 months). Gonadotropins induced significant increases in testicular volume, penile size, and testosterone in over 98% of analyses. Spermatogenesis rates were higher with hCG + FSH (86%, 95% confidence interval [CI] 82%-91%) as compared with hCG alone (40%, 95% CI 25%-56%). However, study heterogeneity and treatment variability were high. This systematic review provides convincing evidence of the efficacy of gonadotropins for pubertal induction. However, there remains substantial heterogeneity in treatment choice, dose, duration, and outcomes assessed. Formal guidelines and randomized studies are needed.

Pulsatile Gonadotropin-Releasing Hormone Therapy Is Associated With Better Spermatogenic Outcomes than Gonadotropin Therapy in Patients With Pituitary Stalk Interruption Syndrome

ObjectiveTo compare the effects of combined gonadotropin and pulsatile gonadotropin-releasing hormone (GnRH) therapy on spermatogenesis in patients with pituitary stalk interruption syndrome (PSIS). MethodsMale patients with PSIS (N = 119) were retrospectively studied. Patients received pulsatile GnRH therapy (N = 59) were divided into response and poor-response groups based on luteinizing hormone (LH) levels after 1-month treatment with a cutoff value of 1 or 2 IU/L. Participants with gonadotropin therapy were divided into human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) group (N = 60), and patients with pulsatile GnRH therapy were classified into GnRH group (N = 28) with treatment duration ≥6 months. ResultsThe overall success rates of spermatogenesis for hMG/hCG and GnRH therapy were 51.67% (31/60) vs 33.90% (20/59), respectively. GnRH group required a shorter period to induce spermatogenesis (8 vs 15 months, P = .019). hMG/hCG group had higher median total testosterone than GnRH group [2.16, interquartile range(IQR) 1.06-4.89 vs 1.31, IQR 0.21-2.26 ng/mL, P = .004]. GnRH therapy had a beneficial effect on spermatogenesis compared to hMG/hCG therapy (hazard ratio 1.97, 95% confidence interval 1.08-3.57, P = .026). In patients with pulsatile GnRH therapy, compared with the poor-response group, the response group had a higher successful spermatogenesis rate (5.00% vs 48.72%, P = .002) and higher median basal total testosterone (0.00, IQR 0.00-0.03 vs 0.04, IQR 0.00-0.16 ng/mL, P = .026) with LH = 1 IU/L as the cutoff value after 1-month pulsatile GnRH therapy. ConclusionsPulsatile GnRH therapy was superior to hMG/hCG therapy for spermatogenesis in patients with PSIS. Earlier spermatogenesis and higher concentrations of sperm could be obtained in the GnRH group if patients received therapy over 6 months.

Human Menopausal Gonadotropins in Combination for Stimulation does not Improve IVF Outcomes in POSEIDON Group 4 Patients, When Compared to Recombinant Follicle Stimulating Hormone Alone: A Prospective Randomized, Non-Blinded, Controlled Pilot Trial

Human Menopausal Gonadotropins in Combination for Stimulation does not Improve IVF Outcomes in POSEIDON Group 4 Patients, When Compared to Recombinant Follicle Stimulating Hormone Alone: A Prospective Randomized, Non-Blinded, Controlled Pilot Trial

Should the trigger to oocyte retrieval interval be different in progestin-primed ovarian stimulation cycles?

Research questionDoes the trigger to oocyte retrieval interval (TORI) affect oocyte maturation rates differently in progestin-primed ovarian stimulation (PPOS) and gonadotrophin-releasing hormone (GnRH) antagonist cycles? DesignThis was a retrospective cohort study. The interaction between the stimulation protocol and TORI was assessed in a linear mixed effects multivariable regression analysis with oocyte maturation rate as the dependent variable, and stimulation protocol (GnRH antagonist or PPOS), age (continuous), gonadotrophin type (FSH or human menopausal gonadotrophin), trigger (human chorionic gonadotrophin [HCG] or GnRH agonist), TORI (continuous) and days of stimulation (continuous) as the independent variables. Oocyte maturation rate was defined as number of metaphase II oocytes/number of cumulus–oocyte complexes retrieved. The maturation rate was calculated per cycle and treated as a continuous variable. ResultsA total of 473 GnRH antagonist and 205 PPOS cycles (121 conventional PPOS and 84 flexible PPOS) were analysed. The median (quartiles) female age was 36 (32–40) years. Of these cycles, 493 were triggered with HCG and 185 with a GnRH agonist. The TORI ranged between 33.6 and 39.1 h, with a median (quartiles) of 36.2 (36–36.4) hours. Maturation rates were similar between fixed PPOS, flexible PPOS and antagonist cycles (median 80%, 75% and 75%, respectively, P = 0.15). There was no significant interaction between the stimulation protocols and TORI for oocyte maturation. ConclusionsPPOS cycles do not seem to require a longer TORI than GnRH antagonist cycles.

Letrozole use in vitrified single-blastocyst transfer cycles is associated with lower risk of large for gestational age infants in patients with polycystic ovary syndrome.

To evaluate the obstetric and perinatal outcomes of three routine endometrial preparation protocols in women with PCOS who underwent frozen embryo transfer (FET). This was a retrospective study in women with PCOS who underwent FET in an academic reproductive medical center. A total of 2710 cycles were enrolled and classified into three groups according to different endometrial preparation protocols; human menopausal gonadotropin (HMG), letrozole + HMG, or hormone replacement therapy (HRT). The stimulation groups had reduced risks of hypertensive disorders of pregnancy (HDP), large for gestational age (LGA) infants, and cesarean delivery than the HRT group. After adjustment for different confounder combinations in the two models, the frequencies of LGA and HDP in the letrozole + HMG group and the HMG group were still significantly lower than those in the HRT group. The letrozole + HMG group exhibited a reduced risk of LGA than HMG group after adjustment of confounders. A trend toward risk reductions in HDP and LGA was observe in turns of HRT, HMG, and letrozole + HMG groups, and the trends were statistically significant (Ptrend = 0.031 and 0.001). In patients with PCOS, ovarian stimulation protocols for endometrial preparation are associated with reduced risks of HDP and LGA compared to HRT cycles. The use of letrozole could further reduce risk of LGA compared to HMG only protocol. We propose that ovarian stimulation protocols can be used widely for endometrial preparation in FET cycles in women with PCOS, especially with the use of letrozole.

Bicornuate uterus with recurrent miscarriage treated with Sitagliptin and PRP: A Case Report of a Successful Pregnancy

Research has shown that recurrent miscarriage can be due to loss of endometrial mesenchymal stem-like progenitor cells (eMSC) and excessive decidual senescence. Sitagliptin has been shown to increase eMSC in the endometrial tissue and decrease decidual senescence. Case This is a case report for a 31-year-old woman with a bicornuate uterus who suffered recurrent miscarriages with IVF treatment. IVF treatment was done due to male factor infertility in a modified stimulation protocol using oral clomifene and human menopausal gonadotrophin. A total of 10 blastocysts were cryopreserved. The couple could not afford to do a PGT-A testing on the cryopreserved embryos. Initial three frozen embryo transfers were done in a natural cycle but resulted in biochemical pregnancies. Thyroid function test and Anti-phospholipid Syndrome tests were negative. Her Protein C level was slightly low at 63%. Hysteroscopy showed no abnormalities in both the uterine horns. A fourth embryo transfer was done in a medicated cycle which resulted in no pregnancy. She was started on oral Sitagliptin 100mg once daily for 3 months. Following this, a fifth embryo transfer was done in a natural cycle. Endometrial PRP infusion was done in this cycle. She successfully became pregnant and delivered a baby girl via LSCS in August 2023. Conclusion Sitagliptin can be a cost-effective adjunct treatment for patients with recurrent miscarriage. While the absence of PGT-A may raise questions regarding the underlying cause of her recurrent miscarriages, oral Sitagliptin can be an option in cases of financial constraint or limited resources.

Highly Purified Human Menopausal Gonadotropin (HP-hMG) Versus Recombinant Follicle-Stimulating Hormone (rFSH) for Controlled Ovarian Stimulation in USPredicted High-Responder Patients: A Cost-Comparison Analysis.

Infertility imposes considerable clinical and economic burden, and the high costs of fertility care are a major barrier to payers. This study assessed the cost differences of highly purified human menopausal gonadotropin (HP-hMG) versus recombinant follicle stimulating hormone (rFSH) for controlled ovarian stimulation (COS) protocols in predicted high-responders from the US payer perspective. A discrete event simulation model was built to perform a cost-comparison analysis of HP-hMG versus rFSH in a cohort of predicted high-responders undergoing up to three embryo transfer cycles, informed by efficacy data from the MEGASET-HR trial. The model considered an event-based treatment pathway and transition probabilities were derived from MEGASET-HR. A variable time horizon was employed, and deterministic and probabilistic sensitivity analyses conducted. Subjects undergoing COS with HP-hMG and rFSH demonstrated comparable live birth rates following three in vitro fertilization (IVF) cycles, with 161 live births with HP-hMG and 152 live births with rFSH, per 310 high-responders. The total cost saving per live birth in subjects receiving HP-hMG versus rFSH was US$3024. These cost savings were largely driven by the need for fewer embryo transfers to achieve similar efficacy outcomes and a reduced rate of ovarian hyperstimulation syndrome. Following deterministic sensitivity analysis, HP-hMG remained cost saving in all baseline parameter variations. No parameters led to rFSH providing cost savings when compared with HP-hMG. Comparable clinical outcomes can be achieved at a lower cost when using HP-hMG versus rFSH based COS protocols in a cohort of predicted high-responders. Such cost savings may reduce the economic burden infertility currently presents to US healthcare providers and those seeking fertility care.

The effect of gonadotrophin-releasing hormone agonist versus human chorionic gonadotrophin trigger on pregnancy and neonatal outcomes in Letrozole-HMG IUI cycles

BackgroundGnRHa and hCG are both used for oocyte maturation and ovulation triggering. However, GnRHa have a shorter half-life than hCG, which leads to luteal phase deficiency. Letrozole (LE) has been found to improve the luteal function. Thus, the choice of triggering strategy can be different in intrauterine insemination (IUI) cycles using LE and human menopausal gonadotropin (HMG). The aim of this study was to compare the pregnancy and neonatal outcomes of patients triggered with GnRHa versus hCG versus dual trigger in LE-IUI cycles.MethodsThis retrospective cohort study included 6,075 LE-HMG IUI cycles between January 2010 and May 2021 at a tertiary-care academic medical center in China. All cycles were divided into three groups according to different trigger strategies as hCG trigger group, GnRHa trigger group and dual trigger group. The primary outcome was clinical pregnancy rate. Logistic regression analysis was performed to explore other risk factors for clinical pregnancy rate.ResultsNo significant difference was observed in clinical pregnancy rate between hCG, GnRHa and dual trigger cycles in LE-HMG IUI cycles (P = 0.964). The miscarriage rate was significantly lower in the GnRHa trigger group, and higher in the dual trigger group, compared with the hCG group (P = 0.045). Logistic analysis confirmed that triggering strategy was associated with miscarriage (aOR:0.427, 95%CI: 0.183–0.996, P = 0.049; aOR:0.298, 95%CI: 0.128–0.693, P = 0.005). No significant differences were observed regarding neonatal outcomes between the three groups.ConclusionsOur findings suggested that both GnRHa and dual trigger can be used to trigger ovulation in LE-HMG IUI cycles, but dual trigger must be used with caution.

Dosing Characteristics of Recombinant Human Luteinizing Hormone or Human Menopausal Gonadotrophin-Derived LH Activity in Patients Undergoing Ovarian Stimulation: A German Fertility Database Study

Objectives: The aim of the study was to evaluate dosing of recombinant human luteinizing hormone (r-hLH) or human menopausal gonadotrophin (hMG)-derived medications with LH activity in ovarian stimulation (OS) cycles for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Design: A non-interventional study was performed to analyse data from the German RecDate database (January 2007–December 2011). Participants/Materials, Setting, Methods: Starting/total r-hLH/hMG dose, OS duration/cycle number, r-hLH/hMG initiation day (first day of administration), and population/cycle characteristics were assessed in women (≥18 years) undergoing OS for IVF/ICSI using r-hLH or hMG-derived medications (excluding corifollitropin alfa, clomiphene citrate, letrozole, mini/micro-dose human chorionic gonadotrophin, and urofollitropin alone). Data were summarized descriptively. Results: 67,858 identified cycles utilized medications containing r-hLH (10,749), hMG (56,432), or both (677). Mean (standard deviation) OS duration with r-hLH and hMG was 10.1 (4.43) and 9.8 (6.16) days, respectively. Median (25th–75th percentile) r-hLH starting dose (75.0 [75.0–150.0] IU) was consistent across patients regardless of age, infertility diagnosis, or gonadotrophin-releasing hormone (GnRH) protocol. Median (25th–75th percentile) hMG-derived LH activity starting dose was 225.0 (150.0–300.0) IU, regardless of GnRH protocol, but was lower in women aged <35 years and those with ovulation disorders/polycystic ovary syndrome. Median (25th–75th percentile) total dose for r-hLH (750.0 [337.5–1,125.0] IU) and hMG-derived LH activity (1,575.0 [750.0–2,625.0] IU) varied according to patients’ age, infertility diagnosis, cycle number, and r-hLH/hMG initiation day. GnRH antagonist use resulted in a numerically higher median total hMG-derived LH activity dose than GnRH agonist use. Limitations: The data used in this study were taken from electronic medical records relating to a specific timeframe (2007–2011) and therefore may not accurately reflect current clinical practice; however, it is likely that the differences between the two compounds would be maintained. Additionally, secondary data sources may suffer from uniformity and quality issues. Conclusions: The standard of care for OS cycles is described with respect to IVF/ICSI treatment including an LH component in Germany during the specified timeframe.

P-599 The use of serum test to detect the LH surge in ultrasound-monitored intrauterine insemination (IUI) significantly increases pregnancy rates.

Abstract Study question Could a serum test to detect LH surge in ultrasound-monitored IUI cycle improve pregnancy rates? Summary answer Serum test to detect LH surges with ultrasound monitoring during IUI cycle significantly increased pregnancy rates. What is known already IUI is known as the first line of treatment for infertile couples and is usually administered with human chorionic gonadotropin (hCG) before ovulation with clomiphene citrate (CC) or/and human menopausal gonadotropin (hMG) to ovarian known to stimulate. One of the key factor for IUI is that insemination should be performed close to ovulation time, as there are many reports that sperm injection at the ovulation time has a high pregnancy rates. However, there are still few reports on the optimal timing of ovulation for performing IUI. Study design, size, duration The IUI performed from January 2016 through November 2022 (n = 3187) was included in this study. A total of 875 patients underwent the IUI by inferring LH surge with procedure with serum test, while 2312 patients underwent the procedure IUI without the serum test (control). Participants/materials, setting, methods In this study included 3187 IUI cycle were analyzed. Controlled ovarian hyperstimulation was conducted with CC (100 mg/day) and hMG. Patients were divided into two groups with serum test or not test (control). The serum test group was monitored LH surge by inferring LH peak during IUI cycle. When the sufficient follicular size and endometrial thickness had been reached, hCG was administrated and insemination was performed. Pregnancy rates were compared by Chi-squared test. Main results and the role of chance In each group, there were no significantly difference in age (34.4±3.7 vs. 34.7±3.7 years old) and endometrial thickness (8.8±2.2 vs. 8.9±2.2 mm) for IUI cycle condition. The serum test group was significantly higher clinical pregnancy rates compared to control group (19.0 vs. 15.7 % respectively) during IUI cycle (P &amp;lt; 0.05). In addition, patients were classified according to the history of at least one or more failed IUI cycle. The clinical pregnancy rates was significantly higher in the serum test group than control group (21.6 vs. 10.8 % respectively) who history of at least one or more failed IUI cycle (P &amp;lt; 0.001). Limitations, reasons for caution A limitation of this study has a too small size of the intervention group compared with the control group. Wider implications of the findings In our results, the serum test group had a significantly higher clinical pregnancy rates than the control group. Therefore, detecting a surge in LH with a serum test during the IUI cycle could predict the optimal timing of ovulation and thus increase the pregnancy rates. Trial registration number not applicable

P-646 The effect of profound LH suppression in GnRH antagonist cycles on IVF/ICSI outcomes-A retrospective study of 400 cycles

Abstract Study question Does low pretrigger LH in GnRH antagonist cycles affect the blastulation rates and cumulative live birth rates? Summary answer Low pretrigger LH in GnRH antagonist cycles does not affect the blastulation rates and cumulative live birth rates in frozen embryo transfer cycles. What is known already • There is conflicting evidence that in GnRH antagonist cycles stimulated with recombinant FSH, low serum LH may effect negatively the pregnancy outcomes in fresh embryo transfer.(Benmachiche et al 2019). • Whether the observed effect of low LH is on the embryo or on the endometrial receptivity is not clear. Study design, size, duration • Retrospective observational single centre study with a study population of 400 undergoing IVF/ICSI in between December 2018- December 2021. • Controlled ovarian stimulation in GnRH Antagonist protocol in unselected population &amp;gt; 21yrs old undergoing IVF/ICSI. • Exclusion Criteria- • Long protocol • Flare protocol • Oocyte cryopreservation cycle • Donor oocyte cycle Participants/materials, setting, methods • Controlled ovarian stimulation is done according to the hospital’s standard operations of practice in flexible antagonist cycle with human menopausal gonadotropins and recombinant/urinary follicle stimulating hormone. • When 3 or more follicles &amp;gt;/=17mm, triggered with GnRH Agonist or dual trigger. • Oocyte pick up scheduled at 35-36hrs following trigger. • Serum LH measured at baseline and at trigger. • Clinical and embryological outcomes are assessed in between low serum LH i.e., &amp;lt;1.5MIU/ML and normal serum LH &amp;gt;/= 1.5 MIU/ML. Main results and the role of chance Demographic variables were comparable between both the arms, except that baseline LH is low in subjects with low pretrigger LH. Mean dose of gonadotropins although not statistically significant, is slightly higher in the low pretrigger LH group. Mean duration of stimulation is higher in low pretrigger LH group and is statistically significant. Mean number of oocytes retrieved, mature oocytes, fertilisation rate, number of blastocysts, day5 and day6 blastocyts, good quality blastocysts and cumulative live birth rates are similar between low pretrigger LH and normal pretrigger LH group. Outcomes between low pretrigger LH and normal pretrigger LH- Mean number of blastocysts- 5.02 +/-3.84 vs 4.72 +/-3.82 (p = 0.44) Mean number of day5 blastocysts- 4 (0-14) vs 3.5(0-20) (p = 0.86) Mean number of day6 blastocysts- 1 (0-8) vs 1 (0-9) (p = 0.4) Mean number of good quality blastocysts- 2(0-19) vs 2 (0-17) (p = 0.68 ) Number of cycles with no blastocysts- 11.1 vs 16.1% (p = 0.35) Cumulative live birth rate 47 vs 48% (p = 0.99) SECONDARY OUTCOMES- Mean dose of gonadotropins- 3282+/- 913 iu vs 3119 vs 926iu (p = 0.07) Mean duration of stimulation- 11.67 +/- 1.87days vs 11.09 +/- 2days (p = 0.01) Mean number of oocytes retrieved-14.98+/- 7.14 vs 13.9+/-7.9 (p = 0.15) Mean number of mature oocytes-11.19+/- 5.64 vs 10.43+/-6.44 (p + 0.21) Mean fertilisation rate-10.7+/- 5.47 vs 9.81+/-6.08 (p = 0.12) Limitations, reasons for caution Retrospective design. Outcomes are assessed in frozen embryo transfer cycles, bur are not compared with fresh embryo transfer cycles. Wider implications of the findings The study provides reassuring data that low serum LH on the day of trigger does not affect the blastulation rates, quality of blastocysts and cumulative live birth rates in frozen embryo transfer cycles. Whether frozen embryo transfer can negate the effect of low pretrigger LH, further studies are needed. Trial registration number Not applicable

O-186 The implementation of a novel algorithm for monitoring ovulation in an IVF mixed protocol may simplify stimulation monitoring

Abstract Study question Which patients are eligible to skip ovulation monitoring before day 10 in In Vitro Fertilization (IVF) and what are the financial implications? Summary answer Thanks to our innovative gonadotropin prescription algorithm, patients with low ovarian reserve and maximum ovarian stimulation may not require monitoring until day 10 of IVF. What is known already In most fertility clinics, the standard procedure for IVF is early monitoring on day 6 of ovarian stimulation. Our focus is on personalizing the stimulation protocol by identifying the optimal dose of gonadotropin. With the aid of our unique algorithm, we aim to streamline monitoring. Frequent ultrasound examinations required for IVF can impose restrictions and create a burden for patients, resulting in increased costs for both patients and physicians. Study design, size, duration In a retrospective study conducted from April 2021 to August 2022 at the OVO clinic in Montreal (Canada), participants included all patients over 18 years old who underwent an IVF stimulation cycle utilizing an antagonist protocol and a customized mixed protocol prescription consisting of follitrophin delta and human menopausal gonadotropin, based on the patient's weight and anti-Mullerian hormone level. The sudy was approved by Veritas IRB, an independent ethic committee. Tracking number of study :2023-3189-13659-2 Participants/materials, setting, methods In the study, gonadotropin dosages were assigned either based on our algorithm (group 1) or at the physician's discretion (group 2). Ultrasound and hormonal analysis were performed on day 6. Following the physician's evaluation, adjustments to the gonadotropin dosage were made if necessary. The common trigger criteria was the presence of at least three follicles measuring between 16 and 22mm. Main results and the role of chance The study included 714 patients meeting the inclusion criteria. In group 1, there was a high percentage of patients stimulated with the maximum doses (80.3% compared to 22.5% in group 2). No dosage modifications or incidents of ovarian hyperstimulation syndrome were observed in group 1. Only 4.5% of patients (n = 16) triggered ovulation before day 10 (on day 9). In the non-maximal dose population, patients treated according to the algorithm (group A) experienced significantly fewer changes to the gonadotropin dosage at day 6 compared to patients treated based on the physician's discretion only (group B) (24.6% vs 46.9%, p &amp;lt; 0.001). The dosage of gonadotropins was notably more frequent adjusted in group B (46.9% vs 24.6%, p &amp;lt; 0.001). A higher risk of ovarian hyperstimulation syndrome was significantly more frequent in the non-maximal dose population compared to the maximal dose population (64.6% vs 27.5%, p &amp;lt; 0.01). These findings suggest that ovulation monitoring may not be necessary in the population stimulated to the maximum dose. This could result in 478 ultrasound and blood tests being avoided in the context of this study. Limitations, reasons for caution The data was obtained through a retrospective analysis. However, not monitoring before day 10 could pose a risk of delaying the cancellation of the IVF cycle, resulting in unnecessary treatment continuation. Wider implications of the findings This significant study indicates that, thanks to our algorithm, monitoring only on day 10 would be adequate for patients with low ovarian reserve who are stimulated to the maximum dose. Further validation of this strategy can be conducted through a randomized prospective study or with the use of different gonadotropins. Trial registration number non applicable

P-658 Clinical outcomes from ART in predicted hyperresponders: in-vitro maturation of oocytes versus conventional ovarian stimulation

Abstract Study question Do ongoing pregnancy rates (OPR) differ in predicted hyperresponders undergoing ART after in-vitro maturation of oocytes (IVM) compared with conventional ovarian stimulation (COS)? Summary answer One cycle of IVM is non-inferior to one cycle of COS in women with serum AMH levels &amp;gt;10ng/mL. What is known already Women with high antral follicle count (AFC) and elevated serum AMH levels, indicating an increased functional ovarian reserve, are prone to hyperresponse during ART treatment. To avoid iatrogenic complications of COS, IVM has been proposed as a mild-approach alternative treatment in predicted hyperresponders, including women with polycystic ovary syndrome (PCOS) who are eligible for ART. To date, inferior pregnancy rates from IVM compared to COS have hampered the uptake of IVM by ART clinics. However, it is unclear whether the efficiency gap between IVM and COS may differ depending on the extent of AMH elevation. Study design, size, duration This study is a retrospective cohort analysis of clinical and laboratory data from the first completed highly purified human menopausal gonadotropin (HP-hMG) primed, non-hCG triggered IVM or COS (FSH or HP-hMG stimulation in a GnRH antagonist protocol) cycle with ICSI in predicted hyperresponders ≤36 years of age at a tertiary referral university hospital. A total of 1707 cycles were included between January 2016 and June 2022. Participants/materials, setting, methods Predicted hyperresponse was defined as a serum AMH level &amp;gt;3.25ng/mL (Elecsys® AMH, Roche Diagnostics). The primary outcome was cumulative ongoing pregnancy rate (OPR) assessed 10-11 weeks after embryo transfer. The predefined non-inferiority limit was -10.0%. The analysis was adjusted for AMH strata. Time-to-pregnancy (TTP), defined by the time interval between egg retrieval and date of successful embryo transfer, was a secondary outcome. Statistical analysis was performed using a multivariable regression model controlling for potential confounders. Main results and the role of chance Data from 463 IVM cycles were compared with those from 1244 COS cycles. Women in the IVM group more often had a diagnosis of Rotterdam PCOS (434/463, 93.7%) compared to those undergoing COS (522/1193, 43.8%), were significantly younger (29.5 years vs 30.5 years, p ≤ 0.001), had a higher BMI (25.7kg/m² vs 25.1kg/m², p ≤ 0.01) and higher AMH (11.6ng/mL vs 5.3ng/mL, p ≤ 0.001). Although IVM cycles yielded more cumulus oocyte complexes (COCs) (25.8 COC vs 15.0 COC, p ≤ 0.001), both groups had similar numbers of mature oocytes (MII) (11.9 MII vs 10.6 MII, p = 0.9). In the entire cohort, non-adjusted cumulative OPR from IVM was significantly lower (198/463, 42.8%) compared to COS (794/1244, 63.8%), p ≤ 0.001. When analysing OPR across different serum AMH strata, cumulative OPR in both groups converged with increasing serum AMH, and OPR from IVM was non-inferior compared to COS from serum AMH levels &amp;gt;10ng/mL onwards (113/221, 51.1% [IVM]; 29/48, 60.4% [COS]). Time-To-Pregnancy was shorter in the IVM group compared to COS (11.3 weeks vs 21.0 weeks, p ≤ 0.001). Multivariable regression analysis adjusting for ART type, age, BMI, oocyte number and PCOS phenotype showed that the number of COCs was the only parameter associated with OPR in predicted hyperresponders with a serum AMH &amp;gt;10ng/mL. Limitations, reasons for caution These data should be interpreted with caution as the retrospective nature of the study holds the possibility of unmeasured confounding factors. Patients enrolled in a clinical IVM program received one-to-one care, in contrast with COS patients who received standard care, which may have influenced TTP. Wider implications of the findings Among subfertile women who are eligible for ART, IVM and COS resulted in comparable reproductive outcomes in a subset of women with a serum AMH &amp;gt;10ng/mL. These findings should be corroborated by an RCT comparing both treatments in selected patients with elevated AMH. Trial registration number Not applicable

P-671 Comparing clomiphene citrate/ flexible GnRH antagonist vs ultrashort flare GnRH agonist protocols for controlled ovarian stimulation in poor ovarian reserve patients

Abstract Study question How do Clomiphene citrate (CC)/ flexible GnRH antagonist and ultrashort flare GnRH agonist protocols compare in poor ovarian reserve patients (POSEIDON groups 3 &amp; 4)? Summary answer In poor ovarian reserve patients, irrespective of age, use of CC / flexible antagonist vs ultrashort flare protocol significantly reduces gonadotrophin consumption and stimulation duration. What is known already Poor responders constitute 47% of ART patients and up to 65% of these have diminished ovarian reserve. Despite the various treatment options available, lack of good quality evidence to enable recommendation of a particular protocol or adjuvant continues to pose a challenge to their effective management. The need for multiple stimulations for pooling up embryos also makes effective cost of treatment an added concern in them. Study design, size, duration An open label, multi centric, randomized controlled study was conducted over a period of 1 year recruiting 116 women having AMH &amp;lt;1.2ng/dl and antral follicle count (AFC) &amp;lt;5 who were further analysed in POSEIDON 3 and 4 subgroups. Patients were randomized to 1 of 2 groups for controlled ovarian stimulation. Those with severe endometriosis, adenomyosis, autoimmune or metabolic disorders, sustained hyperprolactinaemia, congenital uterine malformations and with male partners having severe oligoasthenoteratozoospermia were excluded. Participants/materials, setting, methods Group A (55 women) received CC 100mg from D1-D5 with 300 IU human menopausal gonadotrophin (hMG) in a flexible GnRH antagonist protocol. Group B (61 women) underwent ultrashort flare protocol. 1mg leuprolide was administered from D1-D4 and 300 IU hMG given D2 onwards followed by flexible GnRH antagonist administration. Dual trigger with triptorelin and recombinant hCG was administered 35-36 hours before oocyte retrieval. Embryos cultured till D5 were vitrified for transfer at a later stage. Main results and the role of chance The two groups were well matched for baseline characteristics like age, BMI, AMH, duration of infertility, D2 AFC, estradiol and FSH levels. The mean total gonadotrophin consumption (3387.29 + 1082.5 vs 4407 + 1224.2, p value &amp;lt;0.01) and the duration of stimulation (10.71 + 2.52 vs 11.95 + 2.43, p value &amp;lt;0.01) were significantly lower in group A vs group B. The primary outcomes of median number of oocytes retrieved (4 vs 4, p value- 0.71) , M2 rate (3 vs 3, p value-0.91), fertilisation rate were similar in the two groups. The secondary outcomes of oocyte retrieval rate (103.05 + 42.97 vs 97.14 + 42.96, p value- 0.63), FORT (0.81 +0.68 vs 0.96 + 0.48, p value- 0.37) FOI (0.91 + 0.55 vs 0.92+ 0.54, p value 0.92), top quality embryo rate (0.53 + 1.1 vs 0.41 + 0.84, p value 0.61), cycle cancellation rate (26.22% vs 29.09%), implantation rate (23.63% vs 24.59%) and clinical pregnancy rate (21.31% vs 20%) were also similar in group A vs B respectively. A subgroup analysis of POSEIDON 3 versus POSEIDON 4 patients revealed similar outcomes with both the protocols in the two groups. Limitations, reasons for caution Small sample size of the cases limits the current statistical power of the study. Wider implications of the findings CC /flexible GnRH antagonist protocol is an effective alternative to ultrashort flare protocol in patients with poor ovarian reserve irrespective of their age. The lower gonadotrophin dosage required and shorter duration of stimulation observed make it a viable option in patients who might need multiple stimulations for pooling up embryos. Trial registration number Not applicable