Recombinant FSH Research Articles

084 Superstimulation prior to the ovum pick-up with a single dose of recombinant FSH improves in vitro embryo production in Holstein heifers

084 Superstimulation prior to the ovum pick-up with a single dose of recombinant FSH improves in vitro embryo production in Holstein heifers

Evaluation of the Combination of Recombinant FSH and Antioxidant Therapy on DNA Fragmentation Index (DFI) in Infertile Men

Introduction. Medications such as antioxidants and recombinant FSH are prescribed to improve sperm DFI (DNA fragmentation index) and treat infertility. Due to the high cost and duration of medications, in this study, we decided to investigate the effectiveness of combining these two medications with lower doses and in less time, compared to previous studies prescribing them individually, to reduce sperm DFI in infertile men. Methods. This study, a retrospective observational before and after trial, included a group ( <math xmlns="http://www.w3.org/1998/Math/MathML" id="M1"> <mi>n</mi> <mo>=</mo> <mn>94</mn> </math> ) of men aged 18-50 years with <math xmlns="http://www.w3.org/1998/Math/MathML" id="M2"> <mtext>DFI</mtext> <mo>&gt;</mo> <mn>20</mn> <mi>%</mi> </math> suffering from male factor infertility in an andrology clinic in Tehran, Iran, from 2019 to 2020. Patients received the combination of two medications, recombinant FSH every 5 days (75 IU subcutaneously) and an antioxidant every day (selenium, vitamin E, CoQ10, and folic acid) for 2 months. The patient’s sperm DFI and sperm parameters have been measured before and after the medication and were reported in patient’s files. In all patients, we compare the sperm DFI and sperm parameters before and after the treatment to evaluate the effect of the combination therapy. Results. The sperm DFI was significantly reduced ( <math xmlns="http://www.w3.org/1998/Math/MathML" id="M3"> <mi>p</mi> </math> value ≤0.001) in the patients treated by the combined medication. The sperm DFI improvement was 50.16% in the total population. However, there were no significant changes in other sperm parameters such as sperm concentration, total motility, progressive motility, immotile sperms, and abnormal morphology. Total sperm count and nonprogressive motility had significant changes statistically. Conclusion. Sperm DFI is an important indicator for evaluating the quality of semen. In this study, we demonstrate that the combination of recombinant FSH and antioxidants in a shorter time and with lower doses is effective in reducing DFI significantly. But in terms of other sperm parameters, it does not make a significant difference.

A long-acting recombinant FSH supports high-quality mouse follicle development and oocyte maturation in vitro by coordinating somatic and germ cell transcriptomes.

Strategies to maximize individual fertility chances are constant requirements of ART. In vitro folliculogenesis may represent a valid option to create a large source of immature ovarian follicles in ART. Efforts are being made to set up mammalian follicle culture protocols with suitable FSH stimuli. In this study, a new type of recombinant FSH (KN015) with a prolonged half-life is proposed as an alternative to canonical FSH. KN015 supports the in vitro development of mouse follicles from primary to preovulatory stage with higher efficiency than canonical FSH and enhanced post-fertilization development rates of the ovulated oocytes. The use of KN015 also allows us to compare the dynamic transcriptome changes in oocytes and granulosa cells at different stages, in vivo and in vitro. In particular, KN015 facilitates mRNA accumulation in growing mouse oocytes and prevents spontaneous luteinization of granulosa cells in vitro. Novel analyses of transcriptome changes in this study reveal that the in vivo oocytes were more efficient than in vitro oocytes in terms of maternal mRNA clearing during meiotic maturation. KN015 promotes the degradation of maternal mRNA during in vitro oocyte maturation, improves cytoplasmic maturation and, therefore, enhances embryonic developmental potential. These findings establish new transcriptome data for oocyte and granulosa cells at the key stages of follicle development, and should help to widen the use of KN015 as a valid and commercially available hormonal support enabling optimized in vitro development of follicles and oocytes.

Stimulation techniques and protocols for poor responders in IVF cycles, future prospective methods and techniques, precaution programs.

Purpose: To identify trends regarding approaches, currently used by IVF centers in Greece, in order to treat poor responders. Methods: A retrospective evaluation utilizing the results of a web-based survey was performed. Results: Responses from 36 IVF centers via a web-based survey in Greece was conducted to elucidate optimal treatment strategies of poor responders. IVF specialized Doctors of units with a median of 300 IVF cycles per year were asked to anonymously fill in a set of questions on this complex topic. Results were analyzed, treatment strategies or combinations of protocols or adjuvant therapies used were compared. Also compared number of oocytes retrieved, as well as fertility and pregnancy rates among various IVF centers, based on their responses. A total of 36 centers participated in our survey, (from total 59 IVF centers) forming a web-based questionnaire. Due to responses on question if they observe an increase in the prevalence of poor responders ranging from: 1 - 3 % (8.6%, n=3), 4 - 9% ,(11.1% ,n=4), mainly 20% (47.21% ,n=17), but also greater than 20% (33.3% ,n=12) in total of cases treated in Greek IVF centers. Also, the most common age group of poor responders is 40-50 years of age according to 80%(n=29) of respondents. (Table 1). The review of international medical literature compared with answers received to our questionnaire suggests that no ideal treatment stimulation protocol exist. The following protocols have been described and compared:1).Long protocol with Agonist (25.%,n=9)2).Short protocol with Antagonist (52.8%,n=19)3).Short protocol with Agonist (19.4%,n=7)4).Stimulation only with Gonadotropins (5.6%,n=2)5).Natural Cycle (66.7%,n=24)6).Flare-up protocol (13.9%,n=5)7).Duo-Stim Protocol (11.1%9,n=4)8).Delayed start protocol (11.% ,n=4)9).Protocol with cofifollitropine (13.9%,n=5)10). Clomiphene Citrate Protocol with or without Gonadotropins (41.7%, n=15)11). Clomiphene Citrate Protocol with or without Aromatase inhibitors (19.4%, n=7)12).Letrozole with or without recombinant FSH GnRH Antagonist Use (2.8%, n=1)13). Letrozole with Clomiphene Citrate plus FSH &amp; LH (2.8%, n=1)14). Letrozole with FSH &amp; LH plus GnRH antagonist (2.8%, n=1)15).Protocol with Antagonists in combination with Letrozole(27.8%,n=10) . (Table 2). We also represent results regarding the use of adjuvant treatment modalities to further improve results of stimulation cycles such as: a)Oestrogens(52.2%,n=12),b)Growth Hormone (4.3%,n=1),c)Testosterone (8.7%,n=2),d)Co-enzyme Q10 (56.5%,n=13),e)DHEA (78.3%,n=18). (Table 3). All available therapeutic strategies used and according to international literature and in accordance with data derived from Greek IVF centers, oocyte harvesting ranges at low levels, around 2 to 4 oocytes (88.6% ,n=3), 0-1 (8.6%,n=3), 5-8 (11.4%,n=4) and none of the IVF specialists collected more than 8 oocytes. Oocyte quality is also compromised, in (54.3%, n=19) only one oocyte of A quality was harvested, while 2 and 0, 3 or 4 oocytes of A quality were collected in (49.2%,n=15)and(5.7%,n=2).(Table 4.) , according with data fully verifying the term poor responders. Moreover, we observed that abortion rates are increased &gt;20% (41.2%, n=14), 10-20% (29.4%,n=10), 5-10% (11.8%,n=4) and 1-5% (17.6%,n=6) )(Table 5), as well as pregnancy rates are affected 5-10% (29.4%,n=10) and 10-20% (29.4%,n=10) )(Table 6), while percentages of live pregnancies over 20% is observed in (17,6%,n=6) and under 6% in (23.5%,n=8)(Table 7). Conclusion: All responses from the IVF specialists demonstrate the difficulty of treating this heterogenic group of subfebrile women. The egg donation is the treatment with increased success rate in comparison with different used treatments with agonists , antagonists cc, natural cycle, adjuvant treatments , the success rates of treatment in poor responders in IVF stimulation fluctuates from 7 to 24%. Prognosis is further improved if IVF specialist proposes and proceeds timely to the proper individualized therapeutic strategy.

Progestin-primed ovarian stimulation for fertility preservation in women with cancer: A comparative study.

In women scheduled for cancer treatment, oocytes cryopreservation is a well-established procedure. Random start protocols have been a substantial improvement in this setting, allowing to prevent delay in the initiation of cancer treatments. However, there is still the need to optimize the regimen of ovarian stimulation, to make treatments more patient-friendly and to reduce costs. This retrospective study compares two periods (2019 and 2020), corresponding to two different ovarian stimulation regimens. In 2019, women were treated with corifollitropin, recombinant FSH and GnRH antagonists. Ovulation was triggered with GnRH agonists. In 2020, the policy changed, and women were treated with a progestin-primed ovarian stimulation (PPOS) protocol with human menopausal gonadotropin (hMG) and dual trigger (GnRH agonist and low dose hCG) Continuous data are reported as median [Interquartile Range]. To overcome expected changes in baseline characteristics of the women, the primary outcome was the ratio between the number of mature oocytes retrieved and serum anti-mullerian hormone (AMH) in ng/ml. Overall, 124 women were selected, 46 in 2019 and 78 in 2020. The ratio between the number of mature oocytes retrieved and serum AMH in the first and second period was 4.0 [2.3-7.1] and 4.0 [2.7-6.8], respectively (p = 0.80). The number of scans was 3 [3-4] and 3 [2-3], respectively (p<0.001). The total costs of the drugs used for ovarian stimulation were 940 € [774-1,096 €] and 520 € [434-564 €], respectively (p<0.001). Random start PPOS with hMG and dual trigger represents an easy and affordable ovarian stimulation protocol for fertility preservation in women with cancer, showing similar efficacy and being more friendly and economical.

Effects of recombinant FSH (bscrFSH) and pituitary FSH (FSH-p) on embryo production in superovulated dairy heifers inseminated with unsorted and sex-sorted semen

Superovulation is a drug-based method used in cattle to stimulate the ovarian folliculogenesis and the number of oocytes and transferable embryos. The present study aimed to test the effects of recombinant FSH (bscrFSH) and pituitary FSH (FSH-p) on ovarian response and in vivo embryo production in superovulated dairy heifers inseminated with unsorted and sex-sorted semen. Forty healthy Holstein heifers subjected to a superovulation (SOV) protocol by using FSH-p or bscrFSH were divided randomly into four groups: a) FSH-p inseminated with unsorted semen (USP; n = 10), b) FSH-p inseminated with sex-sorted semen (SSP; n = 10), c) bscrFSH inseminated with unsorted semen (USR; n = 10), and d) bscrFSH inseminated with sex-sorted semen (SSR; n = 10). Ultrasonography was carried out on Day 8 (estrus) and Day 15 (embryo collection) to evaluate the ovarian structures [follicles (FL), corpora lutea (CL), and non-ovulated follicles (NOFL)]. Embryonic-derived parameters were scored on Day 15 [total structures collected (TS), unfertilised oocytes (UFOs), total embryos (TEs), transferable embryos (TFEs), freezable embryos (FEs), and degenerated embryos (DEs)]. No differences were observed regarding ovarian structures (FL and NOFL) irrespective of SOV protocol or group assessed (P > 0.05). CL increased in bscrFSH-derived SOV protocol (P < 0.05). On Day 15, the embryonic-derived parameters TEs, TFEs, and FEs decreased in SSP/SSR compared to USP/USR (P < 0.05). Differences were observed regarding UFOs, with a greater number in SSP and SSR (P = 0.01). In conclusion, the bscrFSH-derived SOV protocol showed improved results compared to FSH-p-derived SOV protocol regarding ovarian (CL) and embryo-derived (TFE) parameters irrespective of the type of semen used.

Corifolitropin-Alfa plus Five Days Letrozole Versus Daily Recombinant-FSH in Expected Normo-Responder Patients: A Retrospective Comparative Study

Background: In recent times, different novel GnRH-antagonist protocols with various combinations of gonadotropins and other molecules (e.g., aromatase inhibitors, selective estrogen receptor modulators) have been proposed for expected normal ovarian responders undergoing assisted reproductive treatments. The purpose of this study was to evaluate the effectiveness of a novel ovarian stimulation protocol based on the combination of corifollitropin-alfa plus five days of letrozole in E-NOR women undergoing IVF as compared with a daily recombinant-FSH regimen. Methods: We conducted a retrospective-controlled study on 182 couples undergoing their first IVF attempt. In Group A (experimental), letrozole (2.5 mg daily) was administered from day 2 (up to day 6 of the cycle), followed by corifollitropin-alfa on day 3 and daily recombinant FSH from day 10. In Group B, recombinant FSH from day 2 were administered (150 IU-225 IU daily). Statistical analysis was completed using SPSS Statistics. The primary outcome was the total number of MII oocytes retrieved. Results: Group A showed similar results compared to Group B in terms of MII oocytes, live birth, implantation, and clinical pregnancy rates (p = ns). Nevertheless, the experimental group was associated with a trend towards a higher number of developing follicles, total oocytes, and embryos (p < 0.05) with lower estradiol and progesterone values at ovulation induction compared to Group B, resulting in an increased chance of performing a fresh embryo transfer (p < 0.05). Conclusions: The combination of CFα plus five days of letrozole was associated with a trend towards a higher number of developing follicles, total oocytes, and obtained embryos. Moreover, the experimental protocol resulted in lower estradiol and progesterone values at ovulation induction compared to daily rFSH, with an increased chance of performing a fresh embryo transfer (with no OHSS occurrence). Given the observational design of our study, further well-conducted RCTs are needed.

Using an Interpretable Machine Learning Model to Predict Corifollitropin Alfa Protocol

Background: To demonstrate an interpretable machine learning (ML) model for a clinical prediction of corifollitropin alfa protocol. Methods: The retrospective study involved 1,221 cycles from 1,180 patients undergoing corifollitropin alfa protocol with oocyte retrieval events from a single in vitro fertilization (IVF) center. The ML models were assigned to the following tasks, which are the dosage of corifollitropin alfa, trigger type, the dosage of recombinant FSH (rFSH), the dosage of recombinant LH (rLH), the duration between the follow-up visit (FUV), and oocyte retrieval. Interpretable SHapley Additive exPlanations (SHAP) were selected to analyze the input features. The ranking of the prediction powers from each input feature reveals the level of contribution to the model. Result(s): Two series of interpretable ML models were developed to predict classification tasks and regression tasks. The areas under ROC (AUC) for predicting the dosage of corifollitropin alfa and trigger type were 0.933 ([Formula: see text] CI 0.907–0.958) and 0.891 ([Formula: see text] CI 0.864–0.918), while accuracies were 0.944 and 0.904. The mean absolute errors (MAEs) that predict the dosage of rFSH, the dosage of rLH, and the duration between the FUV and oocyte retrieval were 97.08 IU (rFSH), 105.61 IU (rLH), and 0.45 days. Conclusions: The study demonstrates a set of interpretable ML models predicting tasks involved in corifollitropin alfa protocol. The potential for the clinical application is to provide consistency in corifollitropin protocol adjustments.

Corifollitropin Alfa Compared to Daily Recombinant FSH in in Vitro Fertilization Programmes: A Meta-Analysis of Randomized-Controlled Trials

Background: Corifollitropin alfa (CFA) is a long-acting recombinant follicle-stimulating hormone (rFSH) used for controlled ovarian stimulation (COS). Several studies analyzing the clinical efficacy and safety of CFA compared to daily rFSH during COS have been carried out. The present study offers a meta-analysis of the randomized controlled trials (RCTs) on this topic. Methods: A computerized search of the published literature was carried out using PubMed, MEDLINE, Science direct and Google Scholar databases. The comparison between CFA and daily rFSH treatments during COS were investigated only in RCTs. The primary endpoint of the study is represented by the number of total oocytes retrieved at ovum pick-up. The studies included in the analysis were pooled together in order to estimate the log odds ratio (OR) or the mean difference (MD) along with the corresponding 95% confidence intervals (CI) by using a random effects model. The heterogeneity between the studies was evaluated with the Higgins and Chi-square tests. Results: The study examined a total of twelve RCTs published from 2004 to date and included a total of 4980 patients, with 2664 receiving CFA and 2316 patients receiving daily rFSH for COS. Women treated with CFA had higher number of total oocytes retrieved at ovum pick-up (MD 0.91, 95% CI [0.34, 1.49], p = 0.001), and higher number of metaphase II (MII) oocytes (MD 1.00, 95% CI [0.37, 1.62], p = 0.002) compared to those receiving daily rFSH. There were no significant differences between the two study groups regarding the other outcomes analyzed. The subgroup analysis performed comparing “normal” versus “poor” responders revealed that normal responders receiving CFA showed an higher cancellation rate, with respect to those receiving rFSH. Conclusions: This study shows that COS with CFA results in a higher number of oocytes retrieved at ovum pick-up in comparison with daily rFSH.

Eight weeks of androgen priming by daily low-dose hCG injections before ICSI treatment in women with low ovarian reserve.

Does 8 weeks of continuous low-dose hCG administration increase the proportion of antral follicles that reach the preovulatory state during ovarian stimulation (OS) in women with low ovarian reserve? The proportion of antral follicles (2-10 mm) that reached the preovulatory state did not increase. The administration of androgens prior to OS might upregulate FSH receptor (FSHR) expression on granulosa cells, making follicles more responsive to exogenous FSH stimulation during OS. LH and hCG stimulate the local follicular androgen synthesis in theca cells and may be used as an endogenous androgen priming method. Exogenous priming by testosterone and dehydroepiandrosterone (DHEA) have been shown to increase the number of retrieved oocytes and live birth rate but the studies are small, and their use is associated with side effects. A prospective, paired, non-blinded single-center study including 20 women serving as their own controls conducted between January 2021 and July 2021 at The University Hospital Copenhagen Rigshospitalet, Denmark. Participants underwent two identical consecutive IVF/ICSI treatments, a Control cycle and a Study cycle, separated by ∼8 weeks (two menstrual cycles) of daily injections of 260 IU recombinant hCG (rhCG). A freeze-all strategy was applied in the Control cycle. Both IVF/ICSI cycles were performed in a fixed GnRH antagonist protocol using a daily dose of 300 IU recombinant FSH (rFSH) and GnRH antagonist 0.25 mg from stimulation days 5-6. Follicular output rate, defined as the number of follicles >16 mm on hCG trigger day divided by the antral follicle count (2-10 mm) at baseline, did not increase after 8 weeks of hCG priming (P = 0.8). The mean number of oocytes retrieved was significantly higher after the hCG priming being 4.7 (2.8) vs 3.2 (1.7) in the Study and Control cycle, respectively (P = 0.01). The duration of stimulation was longer in the Study versus the Control cycle (P = 0.05), despite the use of identical hCG trigger criterion and similar diameters of the three biggest follicles on hCG trigger day in the two cycles (P = 0.9). The sample size was small, and the number of oocytes retrieved was not the primary endpoint. Larger studies are needed to confirm this finding. Long-term, low-dose rhCG administration may increase the number of oocytes retrieved during IVF/ICSI in women with low ovarian reserve, but more research is needed before firm conclusions can be drawn. This study was funded by an unrestricted grant from Gedeon Richter. A.P. reports personal consulting fees from PregLem SA, Novo Nordisk A/S, Ferring Pharmaceuticals A/S, Gedeon Richter Nordics AB, Cryos International, and Merck A/S outside the submitted work and payment or honoraria for lectures from Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, Merck A/S, and Theramex and Organon & Co. Grants to the institution have been provided by Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, and Merck A/S and receipt of equipment by the institution from Gedeon Richter Nordics AB is reported. The remaining authors have no conflicts of interest to declare. ClinicalTrials.gov Identifier: NCT04643925.

Follicular fluid biomarkers for prediction of human IVF outcome in women with poor ovarian response

BackgroundThe aim of controlled ovarian stimulation is to achieve an optimal number of mature oocytes to obtain good-quality embryos. High follicular fluid (FF) concentrations of FSH, hCG, and LH promote oocyte maturation and are associated with a higher probability of fertilization. LH concentrations in FF are consistently higher in follicles that will lead to a successful IVF outcome. The levels of some of these FF biomarkers may vary among different ovarian stimulation schemes; however, the effects of corifollitropin alfa, recombinant FSH (rFSH), LH (rLH), and highly purified urinary menotropins uhMG on these biomarkers are still unknown. The objective of this study was to characterize the profile of FF biomarkers (leptin, vascular endothelial growth factor (VEGF), metalloproteinases (MMPs), and NO2−/NO3−) according to three different protocols of controlled ovarian stimulation (COS) in poor ovarian responders (POR) and to evaluate the association between these profiles and clinical outcomes. Three groups of POR patients were examined according to the protocols used.ResultsGroup C showed significant higher levels in all biomarkers (p < 0001). FF samples from Group B had the lowest levels of VEGF and Pro-MMP-9. Group A showed the lowest concentration of pro-MMP-2. The VEGF level and number of captured oocytes were positively correlated in Group C (r = 0.534, p = 0.01). MMP-9 and fertilization rate were negatively correlated in Group C (r = −0.476, p = 0.02). We found negative correlations between proMMP-2 and serum estradiol levels on the day of rhCG administration.ConclusionWe found significant variations in the biomarker concentrations between the different controlled ovarian stimulation schemes used in POR patients. These differences can be potentially explained by the nature and composition of the gonadotropins. Our results support the hypothesis that some of these molecules should be thoroughly investigated as noninvasive predictors of egg quality.

Use of new recombinant proteins for ovarian stimulation in ruminants.

Currently, gonadotropin products (follicle stimulating hormone, FSH, and luteinizing hormone, LH) used in animal reproduction are produced by extraction and purification from abattoir-derived pituitary glands. This method, relying on animal-derived materials, carries the potential risk of hormone contamination and pathogen transmission. Additionally, chorionic gonadotropins are extracted from the blood of pregnant mares (equine chorionic gonadotropin; eCG) or the urine of pregnant women (human chorionic gonadotropin; hCG). However, recent advancements have introduced recombinant gonadotropins for assisted animal reproduction therapies. The traditional use of FSH for superovulation has limitations, including labor requirements and variability in superovulation response, affecting the success of in vivo (SOV) and in vitro (OPU/IVEP) embryo production. FSH treatment for superstimulation before OPU can promote the growth of a homogenous follicular population and the recovery of competent oocytes suitable for IVEP procedures. At present, a single injection of a preparation of long-acting bovine recombinant FSH (rFSH) produced similar superovulation responses resulting in the production of good-quality in vivo and in vitro embryos. Furthermore, the treatment with eCG at FTAI protocol has demonstrated its efficacy in promoting follicular growth, ovulation, and P/AI, mainly in heifers and anestrous cows. Currently, treatment with recombinant glycoproteins with eCG-like activity (r-eCG) have shown promising results in increasing follicular growth, ovulation, and P/AI in cows submitted to P4/E2 -based protocols. Bovine somatotropin (bST) is a naturally occurring hormone found in cows. Recombinant bovine somatotropin (rbST), produced through genetic engineering techniques, has shown potential in enhancing reproductive outcomes in ruminants. Treatment with rbST has been found to improve P/IA, increase donor embryo production, and enhance P/ET in recipients. The use of recombinant hormones allows to produce non-animal-derived products, offering several advantages in assisted reproductive technologies for ruminants. This advancement opens up new possibilities for improving reproductive efficiency and success rates in the field of animal reproduction.

Oral Administration of Spirulina platensis at Early Gestation Modulates Litter Size and the Expression of Inhibin, Insulin, IGF-I, CO Q10, and BMP-15 in Ewes Induced for Twinning.

Gestation in sheep necessitates the support of nutrients to avoid early embryonic mortalities. Therefore, this study investigates the effects of supplementing either L-arginine or Spirulina alga in the first trimester on the pregnancy rate, litter size, inhibin, insulin, IGF-I, CO Q10, and bone morphogenetic peptide 15 (BMP15) in maternal circulation. Animals were offered barley (500 g/head/day, 14% CP), alfalfa hay (1 kg/head/day, 12% CP), clean water, and balanced salt block licks as free choices. Forty Noemi and Najdi ewes were randomly allotted into three groups: control (C, n = 8), L-arginine (ARG, n = 16), and Spirulina (SP, n = 16). All females were implanted with CIDR for ten days. On days 8, 9, and 10, treated ewes were given a protocol comprised of human recombinant FSH at descending doses (50, 50, 40, 40, and 30, 30 IU, A.M, and P.M, respectively). At the fifth dose, animals were given an equivalent dose of hCG (240 IU). After CIDR withdrawal, ewes were exposed to fertile rams for mating. SP-ewes were orally given 50 ml (2%) Spirulina, and ARG-ewes were given 50 ml (35 mg/kg BW) L-arginine daily for 50 days postbreeding. Blood inhibin, insulin, IGF-I, CO Q10, and BMP15 were determined throughout gestation until parturition. The findings indicated that the conception rates were 25, 75, and 87.5% in C, ARG, and SP, respectively (P < 0.05). The percent of ewes giving birth to twins was 0, 25, and 50% in C, ARG, and SP, respectively (P < 0.05). The survival rates were 100, 81.8, and 83.3%, respectively. Birth weight was 5.6, 3.2, and 3.4 kg in C, ARG, and SP, respectively. Weaning weights were 28.3, 25.6, and 27.2 kg in C, ARG, and SP, respectively. BMP-15 was reduced (P < 0.05) in ARG than in C and SP. However, SP decreased (P < 0.05) inhibin more than in C and ARG. ARG and SP increased (P < 0.05) insulin than in C, whereas SP decreased (P < 0.05) IGF-I. SP increased CO Q10 compared with ARG. Ewes bearing twins revealed higher (P < 0.05) IGF-I (8.57 ng/ml) than those bearing singles (4.63 ng/ml); however, BMP-15 was higher in single (796.6 pg/ml) than in twin-bearing (387.5 pg/ml) ewes. In conclusion, providing early-gestating ewes with Spirulina enhances maternal health, productivity, and reproductive outcomes.

Metaphase-II oocyte competence is unlinked to the gonadotrophins used for ovarian stimulation: a matched case-control study in women of advanced maternal age.

An impact of different gonadotrophins selection for ovarian stimulation (OS) on oocyte competence has yet to be defined. In this study, we asked whether an association exists between OS protocol and euploid blastocyst rate (EBR) per metaphase-II (MII) oocytes. Cycles of first preimplantation genetic testing for aneuploidies conducted by women ≥ 35years old with their own metaphase-II oocytes inseminated in the absence of severe male factor (years 2014-2018) were clustered based on whether recombinant FSH (rec-FSH) or human menopausal gonadotrophin (HMG) was used for OS, then matched for the number of fresh inseminated eggs. Four groups were outlined: rec-FSH (N = 57), rec-FSH plus rec-LH (N = 55), rec-FSH plus HMG (N = 112), and HMG-only (N = 127). Intracytoplasmic sperm injection, continuous blastocyst culture, comprehensive chromosome testing to assess full-chromosome non-mosaic aneuploidies and vitrified-warmed euploid single embryo transfers (SETs) were performed. The primary outcome was the EBR per cohort of MII oocytes. The secondary outcome was the live birth rate (LBR) per first SETs. Rec-FSH protocol was shorter and characterized by lower total gonadotrophin (Gn) dose. The linear regression model adjusted for maternal age showed no association between the Gn adopted for OS and EBR per cohort of MII oocytes. Similarly, no association was reported with the LBR per first SETs, even when adjusting for blastocyst quality and day of full blastulation. In view of enhanced personalization in OS, clinicians shall focus on different endpoints or quantitative effects related to Gn action towards follicle recruitment, development, and atresia. Here, LH and/or hCG was administered exclusively to women with expected sub/poor response; therefore, we cannot exclude that specific Gn formulations may impact patient prognosis in other populations.

The use of L-carnitine in male reproductive abnormalities: The available evidence

Dietary health supplements have been increasingly used in the prevention and treatment of chronic disorders. During the previous decades, l-carnitine has been reported to have beneficial effects on male reproductive functions. L-carnitine, a non-protein amino acid produced endogenously in the human body from the essential amino acids lysine and methionine or obtained from exogenous dietary sources. The main natural forms of L-carnitine are Acetyl-L-carnitine and propionyl-L-carnitine. The aim of this paper is to review l-carnitine research findings relevant to its use in male reproductive abnormalities. Treatment of reproductive male abnormalities caused by abnormalities of idiopathic semen quality including oligozoospermia, asthenospermia, and azoospermia include hormonal therapies (Clomiphene citrate, tamoxifen, recombinant FSH, and testosterone undecanoate). Non-hormonal therapies include pentoxifylline, and dietary health supplements including carnitine. Carnitine has the additional advantage of improving associated erectile dysfunction. Conclusion: There is convincing research evidence suggesting that l-carnitine can improve male reproductive and can be useful in the treatment of some form’s male infertility and erectile dysfunction.

238 Superstimulation of Nelore prepubertal heifers using a long-acting recombinant human FSH: effects upon oocyte yield and

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

Hormonal parameters and embryological outcomes of in vitro fertilisation/intra cytoplasmic sperm injection cycles in women using dydrogesterone for the prevention of premature luteinizing hormone surge during ovarian stimulation

Aim. To evaluate the hormonal parameters and embryological outcomes of an ovarian stimulation protocol using dydrogesterone to prevent the premature LH surge in IVF/ICSI programmes.&#x0D; Materials and methods. A prospective study randomised, including 79 women with normal ovarian reserve undergoing ovarian stimulation for IVF/ICSI with recombinant FSH (rFSH) from Day 2 or 3 of the menstrual cycle. To prevent the premature LH surge, participants in Group 1 (n=38) received oral dydrogesterone 20 mg/day from the start of ovarian stimulation until the day of ovulation trigger administration. Participants in Group 2 (n=41) received a GnRH antagonist. We evaluated the starting and total dose of gonadotropins, duration of stimulation, serum levels of LH, oestradiol and progesterone on Day 1 and 6 of stimulation and the day of trigger administration, number of retrieved and mature oocytes, fertilization rate, and the number of blastocysts and cryopreserved embryos.&#x0D; Results. There were no significant differences in most hormonal parameters, characteristics of the ovarian stimulation and embryological outcomes between the two groups. Serum levels of progesterone in the dydrogesterone arm were higher than in the GnRH antagonist arm (2.3 nmol/l [2.03.4] vs 1.5 [1.02.4] nmol/l; p=0.026), but without any impact on the embryological outcomes.&#x0D; Conclusion. Prevention of premature LH surge in ovarian stimulation cycles using oral dydrogesterone may represent a convenient alternative to the conventional use of GnRH antagonists, reducing the number of required injections and potentially increasing the convenience in patients who are not planning a fresh embryo transfer.

The use of L-Carnitine in Male Reproductive Abnormalities: The Available Evidence

Dietary health supplements have been increasingly used in the prevention and treatment of chronic disorders. During the previous decades, L-carnitine has been reported to have beneficial effects on male reproductive functions. L-carnitine, a non-protein amino acid produced endogenously in the human body from the essential amino acids lysine and methionine or obtained from exogenous dietary sources. The main natural forms of L-carnitine are Acetyl-L-carnitine and propionyl-L-carnitine. The aim of this paper is to review l-carnitine research findings relevant to its use in male reproductive abnormalities. Treatment of reproductive male abnormalities caused by abnormalities of idiopathic semen quality including oligozoospermia, asthenospermia, and azoospermia include hormonal therapies (Clomiphene citrate, tamoxifen, recombinant FSH, and testosterone undecanoate).Non-hormonal therapies include pentoxifylline, and dietary health supplements including carnitine. Carnitine has the additional advantage of improving associated erectile dysfunction. Conclusion: There is convincing research evidence suggesting that l-carnitine can improve male reproductive and can be useful in the treatment of some forms male infertility and erectile dysfunction.

Comparison of blastocyst euploidy rates following luteal versus follicular phase stimulation in a GnRH antagonist protocol: a prospective study with repeated ovarian stimulation cycles.

Is there any difference in the mean number of euploid embryos following luteal phase start (LS) and follicular phase start (FS) of ovarian stimulation? The mean number of euploid blastocysts is equivalent independent of whether the inseminated oocytes are derived from FS or LS. Starting ovarian stimulation at any time of the cycle ('random-start') is commonly used for emergency fertility preservation in cancer patients. A few retrospective studies have been published evaluating LS in women undergoing ovarian stimulation in the context of IVF, but there is a lack of robust data on the comparative efficacy of LS versus FS.Although 'random start' is commonly used in cancer survivors, few retrospective and uncontrolled studies have been published evaluating luteal phase stimulation in women undergoing ovarian stimulation in the context of IVF. Owing to this evident lack of robust data on the efficacy of LS, guidelines typically recommend the LS approach only for medical reasons and not in the context of IVF. This is a prospective, equivalence study, with repeated stimulation cycles, conducted between May 2018 and December 2021. Overall, 44 oocyte donors underwent two identical consecutive ovarian stimulation cycles, one initiated in the FS and the other in the LS. The primary outcome of the study was to evaluate whether FS and LS in the same patient would result in equivalent numbers of euploid embryos following fertilization of oocytes with the same sperm sample. Overall, 44 oocyte donors underwent two consecutive ovarian stimulation protocols with 150 μg corifollitropin alpha followed by 200 IU recombinant FSH (rFSH) in a fixed GnRH antagonist protocol. The only difference between the two cycles was the day of initiation of ovarian stimulation, which was in the early follicular phase (FS) in one cycle, and in the luteal phase (LS) in the other. Forty-four oocyte recipients participated in the study receiving a mean of six metaphase II (MII) oocytes from each stimulation cycle (FS and LS). All MIIs were inseminated with the corresponding recipient's partner sperm (which had been previously frozen) or donor sperm, in order to safeguard the use of the same sample for either the FS or LS. Following fertilization and blastocyst culture, all generated embryos underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuploidy). FS resulted in a significantly shorter duration of ovarian stimulation (difference between means (DBM) -1.05 (95% CI -1.89; -0.20)) and a lower total additional dose of daily rFSH was needed (DBM -196.02 (95% CI -319.92; -72.12)) compared with LS. The donors' hormonal profile on the day of trigger was comparable between the two stimulation cycles, as well as the mean number of oocytes (23.70 ± 10.79 versus 23.70 ± 8.81) (DBM 0.00 (95% CI -3.03; 3.03)) and MII oocytes (20.27 ± 9.60 versus 20.73 ± 8.65) (DBM -0.45 (95% CI -2.82; 1.91)) between FS and LS cycles, respectively. Following fertilization, the overall blastocyst formation rate was 60.70% with a euploid rate of 57.1%. Comparisons between the two stimulation cycles did not reveal any significance differences in terms of fertilization rates (71.9% versus 71.4%), blastocyst formation rates (59.4% versus 62%) and embryo euploidy rates (56.9 versus 57.3%) for the comparison of FS versus LS, respectively. The mean number of euploid blastocysts was equivalent between the FS (1.59 ± 1.30) and the LS (1.61 ± 1.17), (DBM -0.02 (90%CI -0.48; 0.44)). The study was performed in young, potentially fertile oocyte donors who are patients with high blastocyst euploidy rates. Although results may be extrapolated to young infertile women with good ovarian reserve, caution is needed prior to generalizing the results to infertile women of older age. The current study provides evidence that initiation of ovarian stimulation in the luteal phase in young potentially fertile women may result in a comparable number of oocytes and comparable blastocyst euploidy rates compared with follicular phase stimulation. This may imply that in case of a freeze-all protocol in young patients with good ovarian reserve, clinicians may safely consider initiation of ovarian stimulation during the luteal phase. This research was supported by an unrestricted grant from MSD/Organon. N.P.P. has received Research grants and honoraria for lectures from: Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins Intenational, Roche Diagnostics, IBSA, Theramex, Gedeon Richter. F.M., E.C., M.R. and S.G. declared no conflict of interests. The study was registered at Clinical Trials Gov (NCT03555942).

Comparison of recombinant human FSH biosimilar QL1012 with Gonal-f® for ovarian stimulation: a phase-three trial

Research questionAre QL1012 and Gonal-f® equivalent in women undergoing ovarian stimulation for assisted reproductive technology (ART)? DesignThis multicentre, randomized, assessor-blinded, phase-three trial was conducted at 13 centres in China. Eligible patients were infertile women; age 20–39 years; body mass index 18–30 kg/m2; regular menstrual cycles; and indication for ART. After successful pituitary downregulation, patients were randomly assigned (1:1) to receive QL1012 or Gonal-f®, stratified by age (initial dose of 75–150 IU for women younger than 30 years, 150–225 IU for women aged 30–34 years and 225–300 IU for women aged ≥35 years, subcutaneously, once daily). The primary end point was the number of oocytes retrieved. ResultsBetween October 2018, and June 2019, 341 patients were included in the per-protocol set. The mean numbers of oocytes retrieved were 14.7 ± 7.0 in the QL1012 group (n = 169) and 13.4 ± 6.1 in the Gonal-f® group (n = 172). Adjusted by analysis of covariance model, the least-squares mean difference was 1.3 oocytes (95% CI –0.1 to 2.7; P = 0.0650), within the pre-defined equivalence margins of ±3.0. Similar results were observed in the full analysis set. Additionally, no statistical differences were found in secondary end points except oestradiol concentration (median 3948.0 pg/ml versus 3545.3 pg/ml; P = 0.0015). Ovarian hyperstimulation syndrome (12.4% versus 13.1 %) and other adverse events were similar between the two groups. ConclusionsTherapeutic equivalence and similar safety profiles were demonstrated between QL1012 and Gonal-f® in women undergoing ovarian stimulation for ART.