Institute for Reproductive Medicine

BackgroundAround 20% of patients undergoing assisted reproductive technology are at risk of hypo-response to ovarian stimulation. The aim of this study was to describe the real-world use of follitropin delta for ovarian stimulation in these patients, as defined by POSEIDON groups 3 and 4 [an anti-Müllerian hormone (AMH) level of <1.2 ng/ml].Materials and methodsThis study was a post-hoc analysis of participants from DELTA, a multi-centre, prospective, observational study conducted in normal care settings in fertility clinics at 14 active sites in France. A subset of 35 patients at risk of hypo-response to ovarian stimulation (mean AMH 0.7 ± 0.29 ng/ml) and treated with follitropin delta were included. Patients were followed for 10–11 weeks after the first fresh or frozen embryo transfer in case of subsequent pregnancy, and data on real-world follitropin delta use collected.ResultsMost patients (92.9%) had undergone their first IVF or ICSI. The prescribed daily dose was usually based on the approved algorithm (N = 26; 74.3%) with a mean daily dose of 14.2 ± 4.1 mcg, resulting in a mean total dose of 187.7 ± 135.6 mcg. The mean duration of ovarian stimulation was 11.6 ± 6.7 days with no premature discontinuations, while the mean number of oocytes retrieved among patients that started stimulation was 6.3 ± 4.3. A fresh transfer was performed for 21 patients (84.0%), with a mean of 1.04 ± 0.98 embryos transferred per patient. Seven patients (20.0%) achieved an ongoing pregnancy (28% per transfer). No adverse drug reactions were reported.ConclusionsThe results describe the real-world use of follitropin delta and demonstrate its suitability for POSEIDON group 3 and 4 patients. These data complement clinical trial outcomes, supporting clinician decision-making and improving IVF/ICSI outcomes.

ObjectiveTo describe the use, efficacy and safety profile of follitropin delta in women undergoing IVF/ICSI in routine clinical practice after one treatment cycle. Study designThis was a French multicenter, prospective, observational study conducted in 14 fertility centers between June 2020 and June 2021. During this period, 248 women undergoing IVF or ICSI were treated with follitropin delta for the first time. Women were followed up to 10–11 weeks after the first fresh or frozen embryo transfer. The main outcomes were use of dosing algorithm, follitropin delta dosing patterns, ovarian response, pregnancy, and adverse drug reactions in routine clinical practice. ResultsThe analyzable population consisted of 223 patients with mean ± SD age of 33.0 ± 4.4 years, body weight of 65.7 ± 11.8 kg, and the median (IQR) AMH level was 2.6 (1.5–4.0) ng/mL. For 193 patients (86.5 %) it was the first IVF/ICSI cycle and for 30 (13.5 %) the second. The algorithm was used for the calculation of the starting dose for 88.3 % of the patients. The mean daily starting dose of follitropin delta was 11.4 ± 4.1mcg for the whole analyzable population and 14.4 ± 5.2 mcg for the sub-group of 26 patients dosed without the algorithm. The mean duration of stimulation with follitropin delta was 10.8 ± 5.2 days. The mean total dose of follitropin delta administered was 122.2 ± 80.0 mcg. An antagonist protocol was used in 90.3 % of patients. The mean ± SD number of oocytes retrieved among patients that started stimulation was 11.3 ± 6.8 and 46.1 % of patients achieved the targeted response of the algorithm of 8–14 oocytes retrieved. A fresh transfer was performed for 77.6 % of patients; the mean ± SD number of embryos transferred was 1.3 ± 0.5. The implantation rate was 36.0 %. Per started cycle, clinical pregnancy was reported in 35.0 % of the patients and ongoing pregnancy in 29.6 %. In total, 5 patients (2.2 %) reported an event of OHSS. ConclusionClinical results as collected in routine clinical practice are promising, showing a favorable effectiveness-safety profile of follitropin delta for a very varied patient population (including anovulatory PCOS, very poor responders, or non-IVF naïve patients). These real-world data complement results from clinical trials and provide useful information for usual clinical practice within a heterogeneous population group.

Abstract The objective of this retrospective study is to clarify the cumulative live-birth rates (CLBRs) from frozen–thawed embryo transfer without preimplantation genetic testing for aneuploidy (PGT-A) to evaluate the validity of infertility treatment in women of advanced reproductive age. A total of 1,011 patients aged ≥ 40 years undergoing their first nondonor in vitro fertilization without PGT-A at our hospital between January 2010 and September 2017 were included. They were followed up for up to two years, or until either treatment discontinuation or a pregnancy that resulted in a live birth. We also estimated the cost per live birth (LB) for each number of transfer cycles. The 2-year CLBRs were 55.6%, 39.0%, 31.3%, 19.1%, 10.6%, 4.4%, and 0% for patients of ages 40, 41, 42, 43, 44, 45, and &gt; 46, respectively. In approximately 80% cases of LB, the patients aged 40–42 and 43–44 years became pregnant by the fourth and second transfer, respectively. The cost per LB exceeded $150,000 after the fourth, third, and second transfers at the age of 40, 41, and 42–43 years, respectively. Patients who showed no results after a certain number of transfers should be advised to quit fertility treatment.

Background: Pregnancy has been one of life’s great mysteries. The endometrium is where life begins, and a receptive endometrium lies at the crossroads of menstruation and pregnancy. Aim of the study: To evaluate the effects of different medical drugs used routinely to improve endometrial thickness, vascularity, and pregnancy rates and to find out the best medical protocol could be used to improve endometrial thickness, vasculature, and pregnancy rate for patient with thin and poorly vascularized endometrium regardless the cause. Materials and methods: The study was carried out on 200 infertile women who have thin , poorly vascularized endometrium, after they matched the inclusion and exclusion criteria , those patients were divided randomly into five groups ; 40 patient in each group, group A received esterofem oral 2mg tablet every 12 hours from day 2 of menstrual cycle till the day of ovulation trigger , group B received vagifem vaginal tablets 25 microgram from the fourth day of menstrual cycle for 15 days or till the day of ovulation trigger, group C received sildenafil citrate gel 3 gm which containing 37.5 mg sildenafil every 12 hours from the 2nd day of menstruation till the day of ovulation trigger.

Abstract Study question Do altered vaginal microbiota, and vaginal leukocytosis, both estimated by the Nugent score, influence live birth rates in IVF after a fresh embryo transfer? Summary answer In our series, Nugent score is able to diagnose Bacterial Vaginosis and predict its bad influence in live birth rates after fresh embryo transfer. What is known already For several years, special attention has been given to vaginal microbiota and vaginosis as part of IVF and embryo implantation failure. Lactobacillus is recognized as dominant in a healthy vaginal microbiota environment while gardnerella is more present in a vaginal microbiota altered and bacterial vaginosis. While all published studies are mostly meta-analysis, the originality of our study is the number of patients (967) tested in a single laboratory and taken care of by one center only. This study also reports the influence of the microbiota and leucocytosis on LBR. Study design, size, duration This study is a retrospective, a non-interventional monocentric cohort study conducted between January 2017 and December 2019. 967 patients benefited from Nugent score for bacterial vaginosis before the start of treatment or within the first week of injections for IVF protocol. No patient was treated by antibiotics. Participants/materials, setting, methods The swab obtained during speculum examination and smeared onto a glass-slide was left to dry at room temperature and then Gram Stained and Nugent score were calculated according to recommendations (Nugent et al., 1991). Bacterial Vaginosis (BV) was diagnosed for Nugent scores of 7 –10 (Group 3) and a score of 4 – 6 (Group 2) was considered intermediate flora (Nugent et al., 1991).In the same way, presence and abundance of leukocytes were recorded. Main results and the role of chance BV prevalence estimated by Nugent score in the total population is of 6.52% (63/967). There is no difference between the three Nugent groups regarding demographics criteria. BV in endometriosis population is of 8.07% (18/223), in patients with tubal infertility 10.46% (18/172) and in patients with male infertility 5.51% (17/353). The presence of Lactobacillus depends on the age and it is (p = 0.4) statistically more present in older patients while the presence of gardnerella depends on infertility indication. Gardnerella is more represented in tubal indications and the difference is statistically significant (p = 0.01). Concerning leukocytosis (numerous, relatively numerous and few leukocytes) or no (rare leukocytes) the difference is statistically significant between pregnancy and failure after embryo transfer (p = 0.014). Leukocytosis is more involved in vagina when the IVF failed. BV prevalence in patients who became pregnant after embryo transfer is of 3.47% (8/230) while BV in patients with IVF failure is of 7.22% (48/664) (p = 0.05). Concerning Live Birth rate, there are statistically significant differences between Group 1 (152/192) and Group 2 (14/24) (p = 0.03), and between Group 1 and Group 3 (8/16) (p = 0.01) but no difference between Group 2 and 3 (p = 0.74). Moreover, in tubal indications, the presence of gardnerella is significantly associated with miscarriage (p = 0.001) Limitations, reasons for caution Our study is retrospective, which may introduce several biases despite the size of our sample i.e all infertility etiologies were included and no differences were made based on the ethnic origins of the patients, which may have resulted in biases. Wider implications of the findings Nugent score is able to diagnose BV and predict its bad influence in both etiology of infertility and pregnancy outcome after fresh embryo transfer. Nugent score allows to define intermediate group and vaginal leukocytosis to which special attention should be paid as it may compromise a pregnancy. Trial registration number NOT APPLICABLE

It is well known that oocyte quality is essential in the determination of the developmental potential of the fertilized oocytes. The oocyte developmental potential decreases in all species with increasing age. Use of serum and follicular fluid concentration of GDF9 as biomarkers of oocyte and embryo quality and their relation to pregnancy rate. Eighty-eight women were included in this study are selected from those undergoing intra-cytoplasmic sperm injection. Positive pregnancy was achieved by 14 women. The difference in mean serum and follicular GDF9 between pregnant and non-pregnant women was not significant. MI oocyte count was not significantly correlated to serum and follicular GDF9 (p &gt; 0.05). MII oocyte count showed a nonsignificant correlation to serum and follicular GDF9 (p &gt; 0.05). Grade 1 embryo count showed a non-significant correlation to serum and follicular GDF9. Grade 2 embryo count showed a non-significant correlation to serum and follicular GDF9. Also, grade 3 embryo count showed a non-significant correlation to serum and follicular GDF9. The current study revealed that serum and follicular GDF9 could not be used as indicators for oocyte maturity, embryo quality, or pregnancy rate

Metformin is an anti-hyperglycemic medication used to treat type 2 diabetes mellitus. Regardless of its anti-diabetic effect, metformin has a non-genomic action and it could be a beneficial additive to treat the sperm which considered as transcriptionally dormant cell and also a molecule that could rapidly adjust the metabolism of spermatozoa to adapt it to the surrounding environment. Sixty-four normozoospermic semen sample included in the study. Each sample incubated for 30 minutes with metformin (2.5 and 0.5 µM) and SFA was conducted to each sample. There was a significant decrease in total motility (progressive and nonprogressive) in samples incubated with both concentrations compared with the neat samples. While the samples incubated with 0.5 µM shows a lower motility compared with 2.5 µM. Metformin significantly reduced total motility of fresh spermatozoa at both concentrations.

Background:The natural cycle (unstimulated cycle) was used in first IVF trial which give birth of a life baby. However, it was soon recognized that the success rate of IVF in natural cycles was low, this may be due to the low number of oocytes retrieved. Ovarian stimulation using urinary gonadotropins was applied to deal with this problem, resulting in a significant increase in both the number of eggs retrieved, as well as the success rate of IVF. But in the same time the using of stimulation drugs may negatively affect oocyte and embryo quality which could diagnosed by using non invasive procedure like measurement of miRNA- 320 in follicular fluid. Aim of study:To compare the effect of stimulation protocol on ICSI outcome using miRNA- 320 that reflects the embryo quality. Materials and method:This comparative study was done on the embryos of seventy one infertile females who were undergoing Intracytoplasmic sperm injection (ICSI) treatment regardless to the presence or absence of previous trials. These patients were divided into two groups, 45 of them treated with agonist protocol and other 26 patients treated with antagonist protocol. Of the 71 oocytes, there were eight immature oocytes (3 at germinal vesicle (GV) stage, 5 at metaphase I (MI) stage) and three abnormal oocytes, and these were excluded from the following ICSI treatment. Measurement of follicular fluid mi-RNA 320 (which is known biomarker of embryo quality) was done by PCR. Results:The statistical analysis showed no significant correlation between miRNA- 320 levels in follicular fluid and age, BMI, number of dominant follicles, number of oocytes retrieved, number of metaphase I, metaphase II, germinal vesicle, abnormal oocytes and number of fertilized oocytes (2PN). The comparison between miRNA 320 levels in good and bad quality embryos showed highly significant (p&lt;0.001) difference but no significant difference (p&gt;0.05) was found between the different stimulation protocols. Conclusions:The stimulation protocol does not affect the level of miRNA which is molecular marker of embryo quality.