Dose Of Follicle-stimulating Hormone Research Articles

Effect of follicle-stimulating hormone dose on the risk of being classified as suboptimal responders according to the POSEIDON criteria.

The purpose of this study is to investigate the impact of daily follicle-stimulating-hormone (FSH) dose on the likelihood of suboptimal response to ovarian stimulation (OS) for in vitro fertilization (IVF) according to POSEIDON's criteria. A tri-center retrospective cohort study (2015-2017) including women with normal anti-Müllerian hormone (AMH ≥ 1.2ng/mL) and antral follicle count (AFC ≥ 5) values per POSEIDON's criteria, undergoing their first IVF/ICSI cycle using conventional OS (FSH ≥ 150IU/day). Suboptimal response was the retrieval of 4-9 oocytes. In previous research, we detected an AMH ≤ 2.97ng/mL and AFC ≤ 12 as the optimal cut-offs predicting suboptimal response. Therefore, we examined the effect of daily FSH dose (≤ 300IU versus > 300IU) on suboptimal response risk for each AMH and AFC value within these thresholds (AMH between 1.20 and 2.97ng/mL, by 0.01ng/mL increments; and an AFC between 5 and 12, by unit increments). Analysis involved contingency tables and multivariable logistic regression. Included were 4005 patients with AMH and AFC values in the specific range, among whom 2131 (53.2%) were suboptimal responders. Among 177 AMH groups analyzed, apart from three distributed irregularly, daily FSH doses > 300IU versus lower doses (≤ 300IU) did not decrease suboptimal response risk; similarly, higher doses did not decrease risk at the eight AFC values examined (p > 0.05 for all). Using multivariable logistic regression, FSH doses were not associated with suboptimal response risk. Conversely, female age, AMH, AFC, and gonadotropin type were associated with suboptimal response. In women with AMH values between 1.20 and 2.97ng/mL and/or AFC between 5 and 12, FSH dose increase did not decrease suboptimal response risk. Individualizing the gonadotropin regimen and considering LH activity supplementation to FSH may mitigate risks.

Obesity may impair response to ovarian stimulation. A retrospective observational study on oocyte quality.

Ovulatory dysfunction is more common in women with obesity. Body fat distribution is also crucial because anovulatory women have a greater waist circumference and more abdominal fat than ovulatory women of similar BMI. The primary aim of the present study is to determine whether there is a relationship between BMI and reproductive characteristics, including hormonal values, antral follicle count (AFC), endometrial assessment at transvaginal ultrasound evaluation (TVUS) during controlled ovarian stimulation (COS), and oocyte retrieval after Ovum Pick-Up (OPU). Data from a cohort of 183 patients were analyzed and divided into three groups based on weight status: normal weight, overweight, and obesity. Evaluated reproductive characteristics included: age, basal values of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-beta-estradiol (E2), thyroid stimulating hormone (TSH), anti-müllerian hormone (AMH), antral-follicle-count (AFC), duration of COS, E2, and progesterone at the last monitoring, TVUS endometrial thickness at the last monitoring before OPU, FOI after OPU. Additionally, the number of meiosis II oocytes retrieved (MII), the total dose of FSH administered, the ratio between MII and total FSH administered, and OSI were registered. AMH levels were significantly lower in obese patients compared to normal weight and overweight women (1.05 IQR 1.20, 1.58 IQR 2.16, 1.32 IQR 1.38, respectively, p-value = 0.032). When looking at the MII/FSH ratio, the normal weight group showed a median value of 3.3 with an IQR of 4.0, the overweight group showed a median value of 2.3 with an IQR of 1.9, and the obese group had a median value of 2.6 with an IQR of 2.8. Those data were statistically significant (p-value = 0.049). These results emphasize the importance of considering weight status in fertility assessment and treatment planning.

Optimizing oocyte yield utilizing a machine learning model for dose and trigger decisions, a multi-center, prospective study

The objective of this study was to evaluate clinical outcomes for patients undergoing IVF treatment where an artificial intelligence (AI) platform was utilized by clinicians to help determine the optimal starting dose of FSH and timing of trigger injection. This was a prospective clinical trial with historical control arm. Four physicians from two assisted reproductive technology treatment centers in the United States participated in the study. The treatment arm included patients undergoing autologous IVF cycles between December 2022–April 2023 where the physician use AI to help select starting dose of follicle stimulating hormone (FSH) and trigger injection timing (N = 291). The control arm included historical patients treated where the same doctor did not use AI between September 2021 and September 2022. The main outcome measures were total FSH used and average number of mature metaphase II (MII) oocytes. There was a non-significant trend towards improved patient outcomes and a reduction in FSH with physician use of AI. Overall, the average number of MIIs in the treatment vs. control arm was 12.20 vs 11.24 (improvement = 0.96, p = 0.16). The average number of oocytes retrieved in the treatment vs. control arm was 16.01 vs 14.54 (improvement = 1.47, p = 0.08). The average total FSH in the treatment arm was 3671.95 IUs and the average in the control arm was 3846.29 IUs (difference = −174.35 IUs, p = 0.13). These results suggests that AI can safely assist in refining the starting dose of FSH while narrowing down the timing of the trigger injection during ovarian stimulation, benefiting the patient in optimizing the count of MII oocytes retrieved.

Effect of Combined Low Dose Human Gonadotropic Hormone, Follicle Stimulating Hormone, and Testosterone Therapy (LFT Regimen) Versus Conventional High Dose Human Gonadotropic Hormone and Follicle Stimulating Hormone on Spermatogenesis and Biomarkers in Men With Hypogonadotropic Hypogonadism

ObjectiveIn male Congenital hypogonadotropic hypogonadism(CHH), it was observed that lower dose human gonadotropic hormone(hCG) can maintain normal intratesticular testosterone(ITT) levels. We propose this study to compare the Low-Dose hCG, follicle stimulating hormone(FSH), and Testosterone(T) [LFT Regimen] to conventional treatment to induce virilization and fertility. DesignThis open-label randomized pilot study was conducted from June 2020 to December 2021. Subjects and outcome measuresCHH were randomly assigned to either the LFT regimen (Group A)-low-dose hCG (500U thrice per week), FSH(150U thrice per week) and T(100mg biweekly) or conventional therapy(GroupB) with high hCG dose(2000U thrice per week) and the same FSH dose. The hCG dosage was titrated to reduce Anti-mullerian hormone(AMH) by 50% and normalization of plasma T in groups A and B, respectively. The primary objective was to compare the percentage of individuals who achieved spermatogenesis between the two groups. ResultsOut of 30 patients, 23(76·7%) subjects achieved spermatogenesis, and the median time was 12(9-14·9)months. There was no difference in achieving spermatogenesis between the two groups (64·3%vs87·5%,p=0·204), and even the median time for spermatogenesis was similar (15monthsvs12months,p=0·248). Both groups had non-significant median plasma AMH at spermatogenesis,[6·6ng/ml(3·3-9·76) vs 4·41ng/ml(2·3-6·47),p=0·298]. Similarly, the median plasma Inhibin B at spermatogenesis between groups were comparable[152·4pg/ml(101·7-198·0)vs149·1pg/ml(128·7-237·3),p=0·488]. ConclusionsA reasonable approach to induce fertility in male CHH is to initiate combination therapy using FSH, low-dose hCG targeting AMH <6·9 ng/ml, along with T to achieve normal range. Monitoring AMH could serve as a proxy indicator of spermatogenesis.

P-699 High levels of total FSH during COS is detrimental to oocyte development in good responders: results from a three-year retrospective, multicenter study

Abstract Study question Are elevated doses of follicle stimulating hormone (FSH) detrimental to oocyte maturation and the efficacy of ovarian stimulation in good responders? Summary answer Elevated FSH levels reduce the number of oocytes collected from good responders. Patients receiving lower total FSH doses had optimal and higher maturation rates. What is known already There is an inverse relationship between the dose of exogeneous follicle stimulating hormone (FSH) and the number of oocytes retrieved. This relationship is independent of patient age or health and implies that excessive FSH doses administered during artificial reproductive technologies (ART) may be detrimental to oocyte maturation. Study design, size, duration This three-year retrospective, multicenter study included 1,075 oocyte donor cycles performed in three IVF clinics between January 2020 and December 2023 with at least a six-month interval between each cycle. Donors were all considered good responders and divided according to the total dose of FSH received per cycle (n = 289 cycles with &amp;lt;1,700 IU FSH; 400 cycles with 1,700 to 2,900 IU FSH; and 386 cycles with &amp;gt;2,900 IU FSH). Participants/materials, setting, methods The mean oocyte donor age was between 26.13 and 27.45 years old. The mean BMI for all three groups was 21. The association between the total FSH dose and serum anti-Müllerian hormone (AMH) level, follicle-to-oocyte index (FOI), number of oocytes retrieved, and oocyte maturation was assessed using the Student’s t-test (parametric) or Mann-Whitney-U test (non-parametric). Main results and the role of chance There were no significant differences in the mean serum AMH levels (5.31 vs. 5.27 vs. 5.13 ng/mL, respectively) and FOI (81.1 vs. 80.2 vs. 81.5, respectively) of patients who received different total doses of FSH. However, the number of oocytes retrieved from each group was inversely related to the total dose of FSH received (24.4 vs. 22.9 vs. 21.01 oocytes, respectively; p &amp;lt; 0.05) Limitations, reasons for caution Full characterization of the oocytes and their developmental potential was outside the scope of this retrospective study. Wider implications of the findings Gaining a better understanding of the complex interplay of gonadotropins throughout folliculogenesis can help optimize ovarian stimulation protocols to maximize the number of mature and developmentally competent oocytes recovered for clinical use. Trial registration number non applicable

Association between metabolic parameters and embryo production in superovulated dairy cattle.

This study aims to investigate the relationship between metabolic parameters and the number of embryos produced in superovulated cows with high genetic characteristics in milk yield. Eighteen Holstein donors were treated with classic superovulation protocols, AI and flushing. During superovulation, decreasing doses of FSH (follicle-stimulating hormone) were administered at 12-h intervals for 4 days. Plasma insulin-like growth factor (IGF1), glucose (GLU), beta-hydroxybutyric acid (BHB), non-esterified fatty acid (NEFA), blood urea nitrogen (BUN) and total protein (TP) levels were determined by using an autoanalyzer. The mixed model analysis of variance was used for statistical analysis. As a result, plasma IGF1, BHB and BUN had significant interactions with both groups and days (p < .05). Additionally, plasma TP-days interactions were significant (p < .05). Furthermore, there was a negative correlation between the number of embryos and plasma BHB levels (p < .05). In conclusion, under appropriate environmental conditions, metabolic profile control of donors can contribute to the embryo production process and to the studies on the metabolic infrastructure.

Impact of maternal age on oxidation-reduction potential in follicular fluid and assisted reproductive technology treatment outcomes

Background: Maternal age influenced the quantity and quality of oocytes. The composition of follicular fluid was changed in advanced maternal age. This study was conducted to evaluate changes in redox potential and blastocyst formation potential in older women. Methods and materials: Retrospective study collected data from December 2020 to October 2023 on patients treated with in vitro fertilization with follicular fluid surveyed at the Center for Reproductive Endocrinology and Infertility (HUECREI), Hue University of Medicine and Pharmacy, Hue. Results: Two cohorts comprised the 456 patients: Group 1, consisting of individuals younger than 35 years of age, and Group 2, comprising those 35 years or older. Anti-Müllerian hormone (AMH), initial follicle-stimulating hormone (FSH), and total FSH dose utilized differed significantly between Groups 1 and 2, with median values of 3.79 versus 2.10 ng/mL (P value &lt; 0.001), 225.00 versus 277.50 IU/L (P value &lt; 0.001), and 2025.00 versus 2325.00 IU/L (P value &lt; 0.001), respectively. However, there were no significant differences in ORP, maturation rate, fertilization rate, or blastocyst formation rate between the two age groups. Variations in ORP were only observed among subgroups of patients with the ability to achieve an expected fertilization rate of ≥ 70% in Group 1. Specifically, the subgroup meeting expectations had a lower ORP of 83.00 ± 83.00 mV, in contrast to the non-expectation group which had an ORP of 96.14 ± 83.00 mV, accompanied by a P value of 0.005. The difference of ORP was not observed in the group that reached and did not reach the benchmark embryo formation ≥ 60% in the two age groups. Conclusion: Advanced maternal age have declined in ovarian function but no statistically significant difference in redox potential in follicular fluid has been observed. The fertilization rate and blastocyst formation rate were equivalent across the two age groups of women. The redox potential of follicular fluid was not statistically significant difference between cycles that reached and did not reach the benchmark of blastocyst formation ≥ 60% in the two age groups of women. Key words: Blastocyst, advanced maternal age, oxidative-reduction potential (ORP), in vitro fertilization.

Poor Response to Gonadotropin Stimulation and Perinatal Outcomes in Fresh In Vitro Fertilization Embryo Transfer Cycles-A Retrospective Cohort Study.

Objective: The objective was to examine the association between poor ovarian response to gonadotropin stimulation for in vitro fertilization (IVF) and adverse perinatal outcomes in singleton gestations in young patients. Methods: This was a retrospective cohort study including women aged 17-39 who underwent fresh embryo transfer and delivered a singleton neonate at a single center (pre-implantation genetic testing excluded) (2007-2022). Patients were classified as one of the following categories: poor responders-daily follicle-stimulating hormone (FSH) ≥ 150 IU yielding ≤ 3 retrieved oocytes; normal responders-4-15 oocytes; and high responders with ≥16 oocytes. The primary outcome was a composite of pre-eclampsia (mild or severe), small-for-gestational-age, gestational diabetes mellitus, and preterm birth (<37 weeks). We compared maternal and neonatal outcomes between the three groups. Multivariable logistic regression was used to control for confounders. Results: Overall, 507 women met the inclusion criteria. Of them, there were 44 (8.68%) poor responders, 342 (67.46%) normal responders, and 121 (23.87%) high responders. Poor responders, compared to normal and high responders, were characterized by a higher maternal age (34.64 ± 4.01 vs. 31.4 ± 5.04 vs. 30.01 ± 4.93, p < 0.001, respectively) and total FSH dosage (3028.41 ± 1792.05 IU vs. 2375.11 ± 1394.05 IU vs. 1869.31 ± 1089.63 IU, p < 0.001). The perinatal outcomes examined, including cesarean delivery (CD) rate and the composite outcome, were comparable between groups. Using multivariable logistic regression and adjusting for ovarian response group, maternal age, nulliparity, and estradiol level and endometrial thickness before ovulation triggering, poor response was not associated with CD rate or the composite outcome, with maternal age associated with CD (p = 0.005), and nulliparity with the composite outcome (p = 0.007). Similar results were obtained when comparing poor responders to each other group separately or to all other responders. Conclusions: Poor ovarian response is not associated with increased adverse maternal or neonatal outcomes.

A Dose-Response Study on Functional and Transcriptomic Effects of FSH on Ex Vivo Mouse Folliculogenesis.

Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and such threshold is moderately variable among individual follicles between 5 and 10 mIU/mL. FSH at 5, 10, 20, and 30 mIU/mL induced distinct expression patterns of follicle maturation-related genes, follicular transcriptomics, and follicular cAMP levels. RNA sequencing analysis identified FSH-stimulated activation of G proteins and downstream canonical and novel signaling pathways that may critically regulate follicle maturation, including the cAMP/PKA/CREB, PI3K/AKT/FOXO1, and glycolysis pathways. High FSH at 20 and 30 mIU/mL resulted in noncanonical FSH responses, including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health.

Is there a preferred time interval between gonadotropin-releasing hormone (GnRH) agonist trigger and oocyte retrieval in GnRH antagonist cycles? A retrospective cohort of planned fertility preservation cycles

BackgroundThe ideal time frame between gonadotropin-releasing hormone (GnRH) agonist (GnRHa) trigger administration and oocyte retrieval in GnRH antagonist cycles has not been well studied. Our goal was to evaluate the effect of this time interval on oocyte yield and oocyte maturation rate in GnRH antagonist cycles designated for non-medical (“planned”) oocyte cryopreservation.MethodsWe conducted a retrospective cohort study including patients who underwent elective fertility preservation, using the GnRH antagonist protocol and exclusively triggered by GnRH-agonist. We focused on the effect of the trigger-to-retrieval time interval on oocyte yield and maturation rate, while also incorporating age, body mass index (BMI), anti-Müllerian hormone (AMH) levels, basal Follicle-Stimulating Hormone (FSH) levels, as well as the type and dosage of gonadotropin FSH medication.Results438 cycles were included. Trigger-to-retrieval time interval ranged from 32.03 to 39.92 h. The mean oocyte yield showed no statistically significant difference when comparing retrievals < 36 h (n = 240, 11.86 ± 8.6) to those triggered at ≥ 36 h (n = 198, 12.24 ± 7.73) (P = 0.6). Upon dividing the cohort into four-time quartiles, no significant differences in the number of retrieved oocytes were observed (P = 0.54). Multivariate regression analysis failed to reveal any significant associations between the interval and the aforementioned variables.ConclusionsThe GnRHa trigger to oocyte retrieval interval range in our cohort did not significantly affect oocyte yield and maturation rate.

Massively Parallel CRISPR-Cas9 Knockout Screening in Sheep Granulosa Cells for FSH Response Genes.

Follicle-stimulating hormone (FSH) regulates ovarian follicle development through specific gene expression programs. Granulosa cells (GCs) are somatic cells surrounding the oocytes, secreting gonadotropins to regulate ovulation and promote follicular development. By analyzing the effects of different doses of FSH on the proliferation of GCs, we found that adding 10 ng/mL of FSH, as the optimal concentration, could promote the growth of GCs. Furthermore, we have successfully constructed the first CRISPR-Cas9 knockout library targeting the genes on chromosomes 2 and 3 and the X chromosomes of the sheep massively parallel coding gene, as well as an ovarian GCs knockout cell library. For the first time, we have exposed the knockout cell library to a concentration of 10 ng/mL FSH to explore the underlying mechanisms. Through this screening, we have identified 836 positive-negative screening genes that are responsive to FSH, thereby revealing the regulatory mechanisms and screening the functionality of candidate genes. Next, RNA-Seq of control (0 ng/mL), low (10 ng/mL), and high (100 ng/mL) doses of FSH revealed 1708 differentially expressed genes, and combined with 836 genes, we obtained 129 FSH dose-dependent genes with extremely significant differences. This enables us to delve deeper into investigating and identifying the mechanisms by which FSH regulates GCs. More generally, we have discovered new regulatory factors and identified reproductivity-associated major effectors. These findings provide novel research directions for further studies on sheep reproduction.

Nonlinear relationship between gonadotropin total dose applied and live birth rates in non-PCOS patients: a retrospective cohort study

The purpose of this article is to explore the relationship between the total dose of follicle-stimulating hormone (FSH) applied during controlled ovulation stimulation and the live birth rates (LBRs) in non-PCOS population. Many studies have found no difference between the dose of FSH application and pregnancy outcomes such as clinical pregnancy rates after fresh embryo transfer. However, a recent large retrospective analysis found a negative correlation between live birth rates and increasing dose of FSH. It is still controversial about the association between FSH dose and LBRs. In addition, no studies have yet explored the nonlinear relationship between FSH and LBRs. This cohort study included a total of 11,645 patients who had accepted IVF/intracytoplasmic sperm injection (ICSI) at the second hospital of Hebei medical university between December 2014 to December 2019. PCOS was identified by Rotterdam PCOS criteria. We researched the association between FSH total dose and live birth rates (LBRs) using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was applied. The analysis of threshold effects indicated that LBR increased with every 1000 IU FSH when the concentration of FSH was lower than 1410 IU (OR 1.55, 95% CI [1.05, 2.28]); however, a negative association between FSH dose and LBR (OR 0.94, 95% CI [0.89, 0.99]) was found when the FSH total dose was higher than 1410 IU. It is worth noting that the relationship between LBR and FSH dose varied among patients of different ages (OR 0.92 vs 1.06, P for interaction < 0.05).

Personalizing the first dose of FSH for IVF/ICSI patients through machine learning: a non-inferiority study protocol for a multi-center randomized controlled trial

BackgroundAdequately selecting the initial follicle-stimulating hormone (FSH) dose during controlled ovarian stimulation (COS) is key for success in assisted reproduction. The objective of COS is to obtain an optimal number of oocytes to increase the chances of achieving a pregnancy, while avoiding complications for the patient. Current clinical protocols do achieve good results for the majority of patients, but further refinements in individualized FSH dosing may reduce the risk of poor ovarian response while also limiting the risk of ovarian hyperstimulation syndrome (OHSS) risk. Models to select the first FSH dose in COS have been presented in literature with promising results. However, most have only been developed and tested in normo-ovulatory women under the age of 40 years.MethodsThis is a randomized, controlled, multicenter, single blinded, clinical trial. This study will be performed in 236 first cycle in vitro fertilization (IVF) and/or ICSI (intracytoplasmic sperm injection) patients, randomized 1:1 in two arms. In the intervention arm, the dose of FSH will be assigned by a machine learning (ML) model called IDoser, while in the control arm, the dose will be determined by the clinician following standard practice. Stratified block randomization will be carried out depending on the patient being classified as expected low responder, high responder, or normo-responder. Patients will complete their participation in the trial once the first embryo transfer result is known. The primary outcome of the study is the number of metaphase II (MII) oocytes retrieved at ovarian pick up (OPU) and the hypothesis of non-inferiority of the intervention arm compared to the control. Secondary outcomes include the number of cycle cancelations (due to low response or no retrieval of mature oocytes), risk of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancy and live birth rates per first transfer.DiscussionTo our knowledge, this is the first randomized trial to test clinical performance of an all-patient inclusive model to select the first dose of FSH for COS. Prospective trials for machine learning (ML) models in healthcare are scarce but necessary for clinical application.Trial registrationClinicalTrials.gov, NCT05948293. Registered on 14 July 2023.

Correlation between the Total Dose of Follicle-Stimulating Hormone and Cumulative Live Birth Rate in Women Undergoing in Vitro Fertilization

Background: Follicle-stimulating hormone (FSH) is widely used during assisted reproductive therapy to facilitate the development of multiple follicles. In turn, the number of oocytes retrieved has been shown to relate to the live birth rate. This retrospective study investigated the correlation between the total FSH dose used and the cumulative live birth rate in individuals who had undergone in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Methods: This retrospective study included women undergoing IVF/ICSI using a gonadotropin-releasing hormone antagonist protocol who had a regular menstrual cycle and an expected normal response to ovarian stimulation. Cumulative live birth rate was defined as the first live birth following the use of all fresh and frozen transfers of embryos derived from one stimulated IVF/ICSI cycle. Results: The analysis included 7,130 stimulated cycles in 6,517 individuals (9,138 transfers). The mean age, antral follicle count, and anti-Müllerian hormone level were [Formula: see text], [Formula: see text], and [Formula: see text][Formula: see text]ng/ml, respectively. The mean total FSH dose, total number of oocytes retrieved, and total FSH dose per oocyte retrieved were [Formula: see text] IU, [Formula: see text], and [Formula: see text] IU, respectively. There was a significant negative correlation between the total FSH dosage and the cumulative live birth rate in women aged [Formula: see text] years ([Formula: see text], 95% confidence interval [−0.14, −0.08]; [Formula: see text]) and in those aged [Formula: see text] years ([Formula: see text], 95% confidence interval [−0.11, −0.02]; [Formula: see text]). Conclusions: The cumulative live birth rate decreased as the total FSH dose increased. These findings suggest that physicians may wish to avoid prescribing a high dose of FSH in women undergoing IVF/ICSI who are predicted not to have a poor response.

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

Serum concentrations of anti-Müllerian hormone modulate ovarian response to different doses of follicle-stimulating hormone in Japanese Black donors.

Anti-Müllerian hormone (AMH) is a marker for predicting embryo production in cows subjected to superovulation; however, it remains to be established as a reliable predictor of reproductive performance. We hypothesized that the serum AMH concentration of donors affects the ovarian response to follicle-stimulating hormone (FSH) treatment during superovulation. Herein, we retrospectively investigated the association between different FSH doses and AMH concentrations in donor Japanese Black cows in a superovulation program and analyzed the number of total and transferable embryos recovered. The number of transferable embryos recovered from donors with high AMH levels was significantly higher than that recovered from donors with low AMH levels. Additionally, it increased further with a reduction in the FSH dose. These results illustrate that the AMH concentration is a useful marker for predicting embryo production after superovulation, and donors with high AMH levels produce more transferable embryos at low FSH doses than at high doses.

Effects of mycobacterium cell wall fraction on embryo development following in vitro embryo production and pregnancy rates following embryo transfer in virgin dairy heifers

An experiment was conducted to determine whether administration of mycobacterium cell wall fraction (MCWF; Amplimune, NovaVive) could enhance embryo developmental competence following in vitro embryo production (IVP) and pregnancy establishment after embryo transfer (ET). Nulliparous, Holstein heifers (n = 40; age 8–15 months) were submitted to two rounds of ovum pick-up (OPU) and IVP in a crossover design. Thirty-six h after follicle wave synchronization, treatments (saline or MCWF, 5 mL, im) were administered in conjunction with a single dose of follicle stimulating hormone (175 IU) and OPU was performed 48–52 h later. Recovered cumulus-oocyte complexes were used for IVP to assess embryo development. For ET, nulliparous, Holstein heifers (n = 225; age 12–18 months) were used as recipients. At 12–24 h after detection of spontaneous estrus, recipients were randomly treated with either saline or MCWF (5 mL, im). The effect of MCWF on pregnancy per ET (P/ET) was assessed in a 2 × 2 factorial design with recipients treated with or without MCWF receiving a fresh IVP embryo from a donor treated with or without MCWF at day 7 or 8 after detected estrus. Blood samples were collected from a subset of donors (n = 8) and recipients (n = 26 to 33 per treatment) prior to treatment and at 6 and 24 h post-treatment to determine serum concentration of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and interferon-γ. Blood samples were also collected from a group of recipients (n = 31 to 39 per treatment) to assess serum concentration of progesterone at days 4, 7, and 16 post-treatment. Pregnancy status was determined at days 40 and 100 of gestation. Donor treatment with MCWF tended (P < 0.07) to increase the proportion of oocytes that developed into transferable embryos, but there was no effect of MCWF on other parameters of embryo development. The P/ET at days 40 and 100 of gestation and pregnancy loss were not affected by donor treatment or recipient treatment with MCWF and there was no interaction. Serum concentration of proinflammatory cytokines among donors and recipients and serum concentration of progesterone among recipients were not increased by treatment with MCWF. Results of the present study indicate that treatment of donors with MCWF has minimal impact on subsequent embryo development following IVP. Moreover, regardless of whether donors or recipients were treated with MCWF, there was no effect on P/ET following transfer of IVP embryos.

Who may benefit from an increased gonadotropin dosing in predicted poor responders undergoing IVF/ICSI? A secondary analysis assessing treatment selection markers of a randomized trial

ObjectiveTo evaluate whether we can identify patient characteristics that serve as treatment selection markers to distinguish which women with expected poor response benefit from increased dosing of follicle-stimulating hormone (FSH) in terms of improving the cumulative live birth rate compared to standard FSH dosing and which women. Study designWe performed a secondary analysis of an RCT performed between March 2019 and October 2021 comparing cumulative live birth after increased dosing (N = 328) who received 225 or 300 IU/day according to their antral follicle count (AFC) and standard dosing (N = 333) who received 150 IU/day of gonadotropin. ResultsThe MFPI analysis showed the benefit of the increased dosing of FSH on cumulative live birth starts to emerge when women were older than 30 years (women > 30 years: 46.5 % vs. 34.2 %; adjusted relative risk (aRR) 1.32, 95 % confidence interval (95 %CI) 1.05–1.66; women ≤ 30 years: 54.7 % vs. 58.6 %; aRR 0.91, 95 % CI 0.72–1.14; p for interaction 0.019). Only those who had AFC between 1 and 3 benefited from the increased FSH dose (AFC 1–3: 38.5 % vs. 6.5 %; aRR 5.88, 95 % CI 1.50–23.15; AFC 4–9: 50.3 % vs. 46.0 %; aRR 1.08, 95 % CI 0.92–1.27; p for interaction 0.023). Expected poor responders defined by the Bologna criteria and POSEIDON criteria did not significantly benefit from the increased dosing of FSH. ConclusionsWomen who are aged >30 years or have AFC 1–3 are likely to benefit from increased dosing of FSH by having a higher cumulative live birth rate.

Population Pharmacokinetic Analysis of Follicle-Stimulating Hormone During Ovarian Stimulation: Relation with Weight, Prolactin and Gene Polymorphism in THADA and ADIPOQ.

Personalisation strategies of ovarian stimulation for in vitro fertilisation (IVF)/ intracytoplasmic sperm injection (ICSI) treatments using exogenous follicle-stimulating hormone (FSH) have been extensively studied over the past 20 years. This research aimed to develop a FSH population pharmacokinetic (PPK) model taking into account the contribution of gene polymorphisms in Chinese reproductive-age women. Data from 173 patients undergoing GnRH agonist down-regulation long protocols of IVF/ICSI treatment were collected. PPK analysis was subsequently conducted using the nonlinear mixed-effect model (NONMEM) software. Several covariates, including 18 single nucleotide polymorphisms, demographic factors and biological characteristics, were evaluated. The final PPK model was extensively validated using bootstrapping and normalised prediction error distribution, as well as external validation on an independent group of 35 patients. FSH PPK was accurately described by a one-compartment model with first-order absorption. The typical population value of apparent clearance was estimated to be 0.81 L/h [relative standard errors (RSE) 5.3%] with an inter-individual variability (IIV) of 16.0%. The typical apparent distribution volume was 8.36 L (RSE 9.7%, 59.7% IIV), and the absorption rate constant was estimated to be 0.0444 h-1 (RSE 9.1%). Body weight, basal prolactin concentration and the gene ADIPOQ (rs1501299) showed a significant covariate effect on the FSH clearance rate and exposure concentration. Genotypes of THADA (rs12478601) significantly influenced the distribution volume. Simulation results indicated that patients with the TT genotype of THADA (rs12478601) required a longer time to reach steady state and had less fluctuation in FSH levels. Model evaluations showed that the final model accurately and precisely described the observed data and demonstrated effective prediction performance. PPK models of FSH have been developed, which could potentially be used for FSH dosage individualisation in the clinical setting. This study has been registered with the Chinese Clinical Trials Registry (ChiCTR2100049142).

Effects of reduced follicle-stimulating hormone dosage before human chorionic gonadotropin trigger on in vitro fertilization outcomes

ObjectiveTo determine whether a reduced dose of follicle-stimulating hormone (FSH) before human chorionic gonadotropin (hCG) trigger during ovarian stimulation can affect in vitro fertilization (IVF) outcomes.MethodsThis study included 347 patients with a normal ovarian response who received a reduced dose of FSH before hCG trigger for 2–3 days (Group A) and 671 patients who did not receive a reduced dose (Group B) from a university-affiliated IVF center between January 2021 and December 2022. The primary endpoint was estrogen (E2) and progesterone (P) levels on the day of hCG trigger, fresh embryo transfer cycles, laboratory outcomes, and clinical outcomes between the two groups.ResultsOn the day of hCG trigger, Group A had significantly lower E2 and P levels than those in Group B (3454.95 ± 1708.14 pg/mL versus 3798.70 ± 1774.26 pg/mL, p = 0.003; and 1.23 ± 0.53 ng/mL versus 1.37 ± 0.59 ng/mL, p < 0.001, respectively). The proportion of patients with P levels ≥ 1.5 ng/mL was 22.48% in Group A compared to 34.58% in Group B (p < 0.001), while the proportion of patients with E2 ≥ 5000 pg/mL was 15.27% in Group A compared to 25.93% in Group B (p < 0.001). The fresh embryo-transfer cycle rate in Group A was higher than that in group B (54.47% and 32.64%, respectively; p < 0.001). Despite the reduction in FSH dosage, there were no significant differences between groups regarding the number of oocytes retrieved, total number of mature oocytes, normal fertilization rate, cleavage rate, Day 3 top-quality rate, implantation rate, pregnancy rate per cycle, and early pregnancy loss rate.ConclusionWhile a reduced dose of FSH prior to hCG trigger during ovarian stimulation did not significantly affect IVF outcomes, it was associated with lower E2 and P levels, resulting in fewer cycles with E2 ≥ 5000 pg/mL and P ≥ 1.5 ng/mL on the day of the hCG trigger.