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To compare assisted reproductive technology (ART) outcomes and preimplantation embryo development between underweight and normal-weight women.This retrospective cohort study included 26 underweight women (body mass index [BMI] 18.50 kg/mThe mean ± standard deviation age of the underweight and normal-weight women was similar (31.6 ± 4.17 vs 32.4 ± 3.59 years;Underweight status has no adverse impacts on the outcomes of IVF/ICSI with either fresh or frozen ET or on preimplantation embryo development and quality.

To examine the effect of the BNT162b, mRNA, SARS-CoV-2 virus vaccine on sperm quality.This was a prospective cohort study conducted on sperm donors at the sperm bank of a tertiary, university affiliated medical center. All sperm donors donated sperm repeatedly and the average sperm parameters of all available samples were compared before and after receiving the SARS-CoV-2 vaccine. Each donor served as his own control. For all participants, at-least one sperm sample was received 72 days after completing the second vaccine. Main outcome measures included total sperm count, total motile count and percent of motile sperm.A total of 898 sperm samples from 33 sperm donors that were vaccinated with the Pfizer BNT162b, mRNA, SARS-CoV-2 virus vaccine were analyzed, 425 samples were received before the vaccine, while 473 samples were received after vaccination. Total sperm count and total motile count increased after the second vaccine compared to samples before vaccination. Percent of motile sperm did not change after vaccine.The Pfizer BNT162b, SARS-CoV-2 vaccine has no deleterious effect on sperm quality. Patients and physicians should be counseled accordingly.

Research question In women at advanced age of 43–45 years undergoing repeated IVF cycles with autologous oocytes, who has the highest chance for birth and who should be referred early to receive donor oocytes? Design A retrospective cohort study was conducted at a university hospital reproductive center. The computerized database of 394 women aged 43–45 undergoing 1528 non-donor IVF or ICSI cycles between 2010 and 2019 was analyzed. a decision tree was developed, enabling a comprehensive study of a set of clinical parameters and the expected outcomes. Results The analysis included the outcomes of 394 women undergoing a total of 1528 cycles. The cumulative clinical pregnancy rate was 15% (59/394) and the cumulative live birth rate was 8.4% (33/394). The decision tree developed to predict women that should be offered egg donation included age, poor ovarian response to stimulation, the number of top-quality embryos, dominant follicles, previous pregnancy or live birth, fertilized oocytes and BMI. The model showed that a good ovarian response in the first cycle was the best predictor for live birth (13.3% gave birth). However, among women with poor responses, 7.1% of those who were younger than 43.5 years gave birth, and none of the women who were older than 43.5 years did. Conclusion Women over 43.5 years old with less than four oocytes collected in their first IVF cycle should be offered ovum donation, since their live birth rate in subsequent cycles is negligible.

Purpose: To compare recombinant FSH (rFSH) with highly purified-human menopausal gonadotrophin (hp-hMG) on ovarian response in women undergoing elective fertility preservation (FP). Methods: This retrospective study included 456 women who underwent elective FP with gonadotropin-releasing hormone (GnRH) antagonist or progestin-primed ovarian stimulation (PPOS) protocols between 01/2017-12/2021. Three-hundred and forty-one women were stimulated with rFSH and 115 with hp-hMG, and the ovarian stimulation outcomes were compared between the two groups. A multivariate linear regression analysis assessed the impact of age, basal FSH level, antral follicle count, and protocol type on the ovarian stimulation outcomes. Results: Women in the rFSH group were significantly younger, and their antral follicle count was significantly higher than those in the hp-hMG group (35.50±2.12 vs. 35.99±2.13 years, P = 0.034 and 13.76±6.08 vs. 11.84±6.06, P = 0.002). There were no significant group differences in the amount (P = 0.645) and duration (P = 0.265) of FSH stimulation. The peak estradiol level was significantly lower for the rFSH group compared to the hp-hMG group (2547.18±1648.21 pg/mL vs. 3468.02±2497.69 pg/mL, P < 0.001), while peak progesterone level was significantly higher (1.33±0.75 ng/mL vs. 1.01±0.52 ng/mL, P = 0.001). The numbers of retrieved and MII oocytes were significantly higher for the rFSH group compared with the hp-hMG group (16.82±10.95 vs. 13.25±9.66, P = 0.02, and 13.22±9.13 vs. 9.76±7.11, P = 0.005), while the maturity rates were comparable (P = 0.103). Conclusion: rFSH was demonstrated to have superior oocyte yield compared to hp-hMG in ovarian hyperstimulation for women undergoing elective FP.

OBJECTIVE To investigate the prevalence of testicular microlithiasis and its association with sperm retrieval rates and histopathology in men with non-obstructive azoospermia. METHODS A total of 120 men underwent scrotal ultrasonography prior to microsurgical testicular sperm extraction. Sperm retrieval rate, testicular histopathology, testicular size, reproductive hormones, karyotyping, Y chromosome microdeletion analyses, and presence of varicoceles and hydroceles were compared between men with and without testicular microlithiasis. RESULTS The total sperm retrieval rate was 40%. Ten men with normal spermatogenesis were excluded. The remaining 110 men with non-obstructive azoospermia were analyzed and testicular microlithiasis was detected in 16 of them (14.5%). The sperm retrieval rate in that subgroup was only 6.2% (1/16) as opposed to 39.4% (37/94) in men with non-obstructive azoospermia and no evidence of microlithiasis (P = 0.009). The mean right and left testicular diameters were significantly lower in the microlithiasis group (P = 0.04). On multivariate logistic regression analysis, the presence of mictolithiasis (odds ratio 7.4, 95% confidence interval 2.3, 12.2; P = 0.01) was the only independent predictor of unsuccessful sperm retrieval. The 15 patients with microlithiasis and without successful sperm extraction were diagnosed by histopathology as having Sertoli cells only. The 16th patient with successful sperm retrieval had a histopathology of mixed atrophy and was diagnosed with Klinefelter syndrome. CONCLUSION The presence of testicular microlithiasis is associated with low sperm retrieval rates among our cohort of men with non-obstructive azoospermia undergoing scrotal ultrasonography prior to microsurgical testicular sperm extraction. Larger, prospective studies should be conducted to confirm these findings.

Research question Is ovarian stimulation and pregnancy in women with familial adenomatous polyposis (FAP)-associated desmoid tumours safe? Design The study included women with FAP-associated desmoid tumours who underwent fertility treatments at the authors’ tertiary medical centre between the years 2011 and 2021. Data were collected from the fertility unit's charts and from the oncological registries. The main outcome measures were the number of vitrified oocytes and embryos, and the number of live births in preimplantation genetic testing for monogenic/single gene defects (PGT-M) cycles. Results Overall, 17 women were identified suitable for this study. A total of 117 mature oocytes were vitrified for fertility preservation and 106 embryos were submitted to PGT-M. One patient returned to claim her cryopreserved oocytes, and five patients who underwent PGT-M embryo transfer reported three live births. A statistically significant decrease in selected fertility cycle parameters was observed in one woman who co-administered sorafenib (a multikinase inhibitor) during her first cycles of treatment, as the mean number of oocytes before and after was 2.7 (±1.3) versus 13.2 (±3.3) (P = 0.02), the mean number of metaphase II oocytes was 2.2 (±2.1) versus 7.7 (±2.6) (P = 0.007), and the mean number of two-pronuclei oocytes was 0.5 (±1.1) versus 3.5 (±1.7) (P = 0.09). Three patients had a median desmoid tumour growth on magnetic resonance imaging of 6.2 (2.9–7.2) cm when compared with prior ovarian stimulation imaging. Conclusions Ovarian stimulation for women with desmoid tumours was characterized in some patients with an acceleration in tumour growth, regardless of the use of aromatase inhibitors. The use of sorafenib should be carefully considered during the course of fertility treatment.

Research question Can patient selection for successful preimplantation genetic testing for women who are fragile X (FMR1) premutation carriers be optimized using a decision tree analysis? This decision support tool enables a comprehensive study of a set of clinical parameters and the expected outcomes. Design A retrospective case–control study analysing the results of 264 fresh and 21 frozen preimplantation genetic testing for monogenic disorders/single gene defects (PGT-M) cycles in 64 FMR1 premutation carriers. Primary outcome was live birth per cycle start. Live birth rate was calculated for the start of the ovarian stimulation cycle. Fresh and frozen embryo transfers from the same cycle were included. Results The decision tree model showed that the number of cytosine guanine (CGG) repeats was only a moderate predictor for live birth, whereas an age younger than 36 years was the best predictor for live birth, followed by a collection of 14 or more oocytes. These findings were supported by the results of the logistic regression, which found that only age and oocyte number were significantly associated with live birth (P = 0.005 and 0.017, respectively). Conclusions The number of CGG repeats is a relatively poor predictor for live birth in PGT-M cycles. FMR1 premutation carriers are no different from non-carriers. Age is the best identifier of live birth, followed by the number of retrieved oocytes.

the application of fertility preservation, initially intended for oncological patients prior to gonadotoxic treatment, has extended in recent years to transgender and gender-nonconforming individuals undergoing therapy for gender compatibility.to examine semen quality and survival in transgender women pursuing semen cryopreservation in the presence or absence of gender affirming hormonal medication.in this retrospective cohort study, we reviewed data of 74 consecutive transgender women presenting for semen cryopreservation at a single center between 2000-2019. Semen parameters before and after cryopreservation were compared to a control group composed of 100 consecutive sperm bank donor candidates. A subgroup analysis of subjects who had used gender-affirming hormonal treatment was also performed.Compared to the control group, transgender women had lower total sperm count (144.0 vs. 54.5 million, respectively, p0.001), lower sperm motility percentage (65.0 vs. 51.0%, respectively, p0.001) and lower total motile sperm count (94.0 vs. 27.0 million, respectively, p0.001). Values were further decreased in transgender women who had received hormonal treatment before sperm cryopreservation. Post-thawing motility rate remained lower in the transgender group compared to the control group (20.0 vs. 45.0%, respectively, p0.001), and the total motile count remained lower as well (2.7 vs. 9.0 million, respectively, p0.001). Following sperm cryopreservation, the post-thaw decreases in total motile sperm count were higher in the transgender group compared with the control group (91.5 vs. 90.0%). Further subdivision in the transgender group showed that the decrease in total motile sperm count was lower for transgender women who did not use gender-affirming hormonal treatment compared to those who did (-89.7% vs. -92.6%, respectively, p0.01).Sperm parameters in transgender women are poor compared to candidates for sperm donation representing the general population. Specimens collected after discontinuation of gender-affirming hormone treatments were further impaired. Moreover, post-thawing sperm total motile count, motility, and overall sperm survival were reduced in transgender women. This article is protected by copyright. All rights reserved.

To analyze whether cleavage stage at compaction, and not only kinetics, can serve as a reliable predictor for clinical outcome.A retrospective cohort study including 1194 embryos, classified by compaction initiation stage (Group 1: compaction at fewer than eight cells, Group 2: compaction at eight cells, Group 3: compaction at more than eight cells). Of these, 815 embryos were evaluated for morphokinetic preimplantation parameters, and 379 embryos were analyzed for clinical implantation following thawing and transfer of single blastocysts during the same period.In total, 1194 embryos were analyzed. Embryos that underwent compaction from more than eight cells (Group 3) exhibited more synchronous cleavage compared with Groups 1 and 2 (at both S2 and S3; P 0.001), and displayed a significantly lower fragmentation rate. The likelihood of obtaining top-quality blastocysts decreased by 73% and 44% when comparing Group 3 embryos with those of Groups 1 and 2, respectively, (P 0.03). Clinical validation of the results shows that while compaction from fewer than eight cells barely produced blastocysts for transfer, compaction at eight or more cells is crucial for implantation and birth (birth rates 11.1% and 18.5% for Groups 2 and 3, respectively).Cleavage stage at compaction has a direct effect on blastocyst quality and subsequent pregnancy, so can be included in newly developed deep learning models for embryo selection.

The purpose of this research is to study the efficacy of GnRH-a versus r-hCG triggering in patients who go through fertility preservation cycles. This retrospective cohort study was performed in a tertiary university-affiliated medical center. It includes 191 patients undergoing fertility preservation cycles between May 2013 and September 2018, in which ovulation was induced by either GnRH-a or r-hCG. Main outcome measures were number and rate of mature oocyte. Among treatment cycles with medical indication, GnRH agonist significantly increases the odds for high mature rate by 3.55 (1.30-9.66), while in treatment cycles with social indication, there is no significant effect of the triggering agent. An advantage for GnRH-a triggering was observed in medically indicated preservation cycles.

The present study aimed to determine the semen quality and cryopreservation outcomes among adolescent transgender females at the time of fertility preservation (FP) before initiating gender-affirming hormone (GAH) treatment. This retrospective cohort study included 26 adolescent transgender females who underwent FP in our Fertility Institute between 06/2013 and 10/2020. Pre-freezing semen parameters were compared to WHO 2010 reference values. Post-thaw semen parameters were used to determine the adequate assisted reproductive technology (ART). A multivariate linear regression analysis was performed to assess the impact of medical and lifestyle factors on semen quality. The mean age at which adolescent transgender females underwent FP was 16.2 ± 1.38 years. The median values of all semen parameters in our study group were significantly lower compared to the WHO data, including volume (1.46 mL vs 3.2 mL, respectively, P = 0.001 ), sperm concentration (28 × 106/mL vs 64 × 106/mL, P < 0.001), total sperm number (28.2 × 106 vs 196 × 106, P < 0.001), total motility (51.6% vs 62%, P < 0.001), and normal morphology (2% vs 14%, P < 0.001). The frequency of semen abnormalities was teratozoospermia 72%, hypospermia 52%, oligozoospermia 28%, and azoospermia 4%. The median post-thaw total motile count was 0.17 × 106/vial, and the quality was adequate only for ICSI in 87.7% of the thawed semen samples. No correlation was found between selected medical and lifestyle factors and poor semen parameters. Semen quality is strongly reduced among adolescent transgender females before hormone therapy and their stored sperm samples are suitable for intracytoplasmic sperm injection (ICSI) rather than conventional IVF/intrauterine insemination (IUI).

Familial adenomatous polyposis (FAP) is an inherited syndrome caused by a heterozygous adenomatous polyposis coli (APC) germline mutation, associated with a profound lifetime risk for colorectal cancer. While it is well accepted that tumorigenic transformation is initiated following acquisition of a second mutation and loss of function of the APC gene, the role of heterozygous APC mutation in this process is yet to be discovered. This work aimed to explore whether a heterozygous APC mutation induces molecular defects underlying tumorigenic transformation and how different APC germline mutations predict disease severity. Three FAP-human embryonic stem cell lines (FAP1/2/3-hESC lines) carrying germline mutations at different locations of the APC gene, and two control hESC lines free of the APC mutation, were differentiated into colon organoids and analyzed by immunohistochemistry and RNA sequencing. In addition, data regarding the genotype and clinical phenotype of the embryo donor parents were collected from medical records. FAP-hESCs carrying a complete loss-of-function of a single APC allele (FAP3) generated complex and molecularly mature colon organoids, which were similar to controls. In contrast, FAP-hESCs carrying APC truncation mutations (FAP1 and FAP2) generated only few cyst-like structures and cell aggregates of various shape, occasionally with luminal parts, which aligned with their failure to upregulate critical differentiation genes early in the process, as shown by RNA sequencing. Abnormal disease phenotype was shown also in non-pathological colon of FAP patients by the randomly distribution of proliferating cells throughout the crypts, compared to their focused localization in the lower part of the crypt in healthy/non-FAP patients. Genotype/phenotype analysis revealed correlations between the colon organoid maturation potential and FAP severity in the carrier parents. In conclusion, this study suggest that a single truncated APC allele is sufficient to initiate early molecular tumorigenic activity. In addition, the results hint that patient-specific hESC-derived colon organoids can probably predict disease severity among FAP patients.

To compare clinical pregnancy rate (CPR) and live birth rate (LBR) after frozen-thawed embryo transfer (FET) of day (D-) 6 blastocysts on D-5 versus D-6. A retrospective cohort study. A university-affiliated single-center tertiary hospital. Women undergoing FET of D-6 blastocysts between August 2015 and March 2019 were included in the study. Exclusion criteria were endometriosis and maternal age ≥ 42. Cycles involving embryo transfer (ET) at D-6 were compared to cycles involving ET on D-5. Primary outcomes assessed were CPR and LBR, and the secondary outcomes were spontaneous abortion and chemical pregnancy rates. Forty-two cycles were assessed, 21 in which ET occurred on D-6 and 21 in which ET occurred on D-5. There were no significant differences between groups regarding age, body mass index (BMI), etiology of infertility, number of oocytes aspirated and blastocysts cryopreserved in the fresh cycle, reason for freezing on D-6, endometrial thickness before ET, and blastocyst grade. A comparison of outcomes of ET on D-5 with those involving ET on D-6 revealed that D-5 transfer produced significantly higher CPR (8, 38% vs. 2, 8.5%; P = 0.030) and LBR (6, 28.6% vs. 1, 4.8%; P = 0.038), respectively. FET of D-6 embryos on D-5 compared with D-6 is associated with increased CPR and LBR values. These findings might be related to the limited time window for optimal rates of implantation and indicate that transferring embryos on D-6 of a FET cycle is likely too late.

Research question In-vitro maturation (IVM) of oocytes recovered during ovarian tissue cryopreservation (OTC) is often practised, although it is still considered experimental. To date, only a few studies have examined the success of this maturation process in pre-menarche girls. The aim of this study was to examine the outcomes of IVM of oocytes recovered during OTC in pre-menarche patients scheduled for onco-therapy. Design A retrospective cohort study in a tertiary university-affiliated hospital. A total of 93 patients aged 0–25 years who underwent OTC as part of onco-fertility preservation between 2007 and 2019 were included in the study. Oocytes were recovered from the medium after OTC and matured over 48 h. Oocyte development and maturation rate were recorded and compared between different age groups. Results Patient's age was not correlated linearly with the total number of mature oocytes R = 0.2. The absolute maturation rate in post-menarche and pre-menarche patients differed significantly (38.0% versus 25.3%, respectively; P > 0.001), whereas the degeneration rate of the oocytes did not (39.8% versus 33.5%; P = 0.167). The pre-menarche group had significantly lower mean number of metaphase II oocytes compared with the post-menarche group (2.8 [±2.3] versus 5.6 [±4.6]; P = 0.01; 95% CI –4.62 to –0.46). Oocytes recovered from patients aged 1–5 years demonstrated low maturation rate. Conclusions Oocytes recovered from pre-menarche girls, and especially those younger than the age of 5 years who undergo fertility preservation, have a lower chance of reaching maturity in IVM compared with older women. This may indicate a need for alternative methods for preserving fertility in these young patients.

Objective To assess the level of satisfaction of women undergoing transvaginal oocyte retrieval (TOR) without anesthesia as well as the comfort of the gynecologists. Design Single-center, prospective cohort study of women undergoing TOR from July 2017 to January 2018. Setting This study was conducted in an academic public hospital. Patient(s) Women with ≤15 follicles for retrieval were eligible. Women with body mass index > 35, difficult vaginal approach, endometrioma > 5 cm, or pelvic inflammatory disease were excluded. Intervention(s) None. Main Outcome Measure(s) Our primary endpoint was patient satisfaction. Secondary endpoints were women’s willingness to recommend or undergo the procedure again without anesthesia, anxiety levels before the procedure, expected level of pain, actual pain levels during the procedure, and gynecologist’s level of difficulty or technical compromise. Result(s) During the study period, 500 TORs were performed, of which 402 (80%) were screened for study eligibility. Overall, data were analyzed for 50 eligible women who had their first in vitro fertilization cycle (participating in the study) without anesthesia. High rates of satisfaction were reported, and 90% would recommend the procedure without anesthesia to their friends. Physicians graded the difficulty of the procedure as very easy in 35 procedures; in only two procedures was difficulty reported. Conclusion(s) TOR without anesthesia is feasible, with a relatively high satisfaction rate from both patients and gynecologists, suggesting that it should be considered in selected women.

Objective To report the first successful oocyte cryopreservation in a prepubertal girl. Design Case report and review of the literature. Setting Tertiary medical center. Patient(s) A 7-year-old prepubertal girl with Turner syndrome mosaicism (45,X[37]/47,XXX[15]) who underwent a novel fertility preservation procedure after fertility preservation counseling and informed decision of the parents. Intervention(s) Controlled ovarian hyperstimulation with daily administration of 100 IU recombinant human follicle-stimulating and 50 IU recombinant human luteinizing hormone per milliliter, injection of 250 μg human chorionic gonadotropin was given 36 hours before the follicular aspiration procedure, and oocytes retrieved by a transabdominal ultrasound guided approach. Main Outcome Measure(s) Mature oocyte cryopreservation. Result(s) The first cryopreservation cycle with use of a gonadotropin-releasing hormone agonist trigger failed to yield oocytes. The second cycle with human chorionic gonadotropin trigger was successful. Six oocytes were retrieved, and all were mature metaphase 2. The patient was discharged in good condition with no complications. Conclusion(s) This novel procedure bypasses the timely physiologic progression of pubertal maturation of the hypothalamic-pituitary-ovarian axis to directly target the ovaries and achieve mature ovarian follicles. This innovative approach offers a new treatment modality for prepubertal girls who need fertility preservation such as in Turner syndrome or in cases that ovarian tissue cryopreservation is contraindicated.

PURPOSE: To compare assisted reproductive technology (ART) outcomes among transgender men with those of fertile cisgender women. METHODS: This retrospective cohort study included 12 transgender men, six with no testosterone exposure and six after testosterone treatment, and 12 cisgender women (oocyte donors) who underwent ART in our institution between June 2017 and December 2019. Statistical analyses compared ART data and outcomes between three groups: cisgender women, transgender men without testosterone exposure, and transgender men after testosterone exposure. Comparisons were also made between transgender men with and without testosterone exposure. RESULTS: The transgender men with no testosterone exposure (23.3 ± 4 years) were significantly younger than the transgender men who had undergone testosterone treatment (30.3 ± 3.8 years; P = 0.012) and the cisgender women (29.1 ± 3.1 years; P = 0.004). The amount of FSH used for ovulation induction (1999 ± 683 mIU/mL) was significantly lower among transgender men without prior testosterone exposure compared with that among cisgender women (3150 ± 487 mIU/mL; P = 0.007). There were no differences in the peak estradiol levels, the number of oocytes retrieved, the number of MII oocytes, and the oocyte maturity rates between the three groups. Five out of six testosterone-treated transgender men underwent embryo cryopreservation, and they all achieved good-quality embryos. CONCLUSIONS: Transgender men have an excellent response to ovulation stimulation even after long-term exposure to testosterone. Oocyte/embryo cryopreservation is, therefore, a feasible and effective way for them to preserve their fertility for future biological parenting.

Women with inflammatory bowel disease (IBD) have an increased risk for adverse pregnancy outcome, so as women using assisted reproduction technology (ART). However, data are scarce regarding the risk imposed by the combination of both. Thus, we aimed to assess pregnancy outcome in these women. A retrospective case–control study, of women with IBD who conceived using ART due to female infertility. The study group (IBD-ART) was matched using propensity score and compared in a 1:1 ratio with three control groups, IBD patients who conceived spontaneously (IBD-SP), women using ART (H-ART) and women who conceived spontaneously (H-SP). The study group comprised of 49 women with IBD conceived via ART that gave birth at our center during the study period. All studied groups did not differ in demographics and obstetric characteristics. IBD groups (both ART and spontaneous) were comparable in disease status prior and throughout pregnancy. Maternal outcome showed no difference regarding preterm birth and pregnancy complications among all studied groups. Women in the IBD-ART group had decreased rates of vaginal delivery (34.7% vs 57.1%, p = 0.032) and higher rates of elective CS (32.7% vs 14.3%, p = 0.048) in comparison to H-SP group, but comparable rates to both IBD-SP and H-ART groups. Neonatal outcomes were comparable among all studied groups. In a sub-analysis by disease type, a higher rate of gestational diabetes was found among ulcerative colitis patients using ART (29.4% Crohn's vs 6.1% UC, p = 0.025). Patients with IBD undergoing ART have comparable pregnancy outcome to women using ART and to patients with IBD with spontaneous pregnancy.

What are the effects of testosterone treatment on oocyte fertilization and preimplantation embryo development among transgender men who have undergone fertility preservation?A retrospective study was undertaken in a university-affiliated tertiary hospital between April 2016 and November 2021. Embryos were divided into three groups by source: 210 embryos from 7 testosterone-exposed transgender men, 135 from 10 cisgender women who cryopreserved embryos, and 276 from 24 cisgender women who underwent fertility treatment. Statistical analyses compared assisted reproductive technology outcomes between the group of transgender men and both groups of cisgender women. Morphokinetic and morphological parameters were compared between the embryos derived from these three groups.The transgender men (30.2 ± 3.5 years of age) were significantly younger than the cisgender women who cryopreserved embryos (35.1 ± 1.8 years; P = 0.005) and the cisgender women who underwent fertility treatment (33.8 ± 3.2 years; P = 0.017). After adjusting for participant age, the fertilization rate was comparable between the transgender men and both groups of cisgender women (P = 0.391 and 0.659). There were no significant differences between the transgender men and the cisgender women who preserved fertility in terms of number of cryopreserved embryos (7.2 ± 5.1 and 3.5 ± 2.6; P = 0.473) or the distribution of embryo age at cryopreservation (P = 0.576). All morphokinetic parameters evaluated by time-lapse imaging, as well as the morphological characteristics, were comparable for the embryos in all three groups.Testosterone exposure among transgender men has no adverse impact upon fertilization rates or preimplantation embryo development and quality.

Does inheritance of the fragile X mental retardation 1 (FMR1) premutation allele affect embryo morphokinetic development?A retrospective cohort analysis of 529 embryos from 126 IVF cycles of 39 FMR1 premutation female carriers undergoing preimplantation genetic testing for monogenic/single gene defects (PGT-M). Morphological and morphokinetic parameters obtained using a time-lapse monitoring system were compared between embryos that inherited the FMR1 premutation allele (FMR1 group, n = 271) and those who received the normal allele (normal group, n = 258). The following embryo outcome measures were compared: morphokinetic parameters up to day 3, start of blastulation time (tSB) for day 5 embryos and the rate of top-quality embryos on days 3 and 5.No differences were found in morphokinetic parameters between the groups from the time of intracytoplasmic sperm injection (ICSI) until a biopsy on day 3. The blastulation rate in the two groups was comparable. However, the start of blastulation was delayed in FMR1 embryos compared to that in the genetically normal embryos (median tSB: 104.2 h [99.3-110.3] versus 101.6 h [94.5-106.7], P = 0.01). In addition, the rate of top-quality FMR1 embryos was lower than that of genetically normal embryos (25.6% versus 38.8%, P = 0.04).Embryos that inherit the FMR1 premutation allele are of lower quality at the blastocyst stage compared with those that do not inherit the mutated allele.

Purpose To compare assisted reproductive technology (ART) outcomes and preimplantation embryo development between underweight and normal weight women. Methods This retrospective cohort study included 26 underweight women (body mass index [BMI] 2) and 104 normal weight women (BMI > 20 and 2) who underwent a total of 204 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles and 358 fresh/frozen embryo transfers (ET) in our institution between January 2016 and December 2018. Statistical analyses compared selected ART outcomes (ovarian stimulation, fertilization, and pregnancy) between both weight groups. Morphokinetic and morphological parameters were also compared between 346 and 1467 embryos of underweight and normal weight women, respectively. Results The mean ± standard deviation age of the underweight and normal weight women was similar (31.6 ± 4.17 vs 32.4 ± 3.59 years; p = 0.323). There were no differences in the peak estradiol levels, the number of retrieved oocytes, the number of metaphase II oocytes, and the oocyte maturity rates between the two groups. The IVF/ICSI fertilization rates and the number of embryos suitable for transfer or cryopreservation were similar for both groups. All morphokinetic parameters that were evaluated by means of time-lapse imaging as well as the morphological characteristics were comparable between low and normal BMI categories. There were no significant differences in pregnancy achievement, clinical pregnancy, live births, and miscarriage rates between the suboptimal and optimal weight women. Conclusion Underweight status has no adverse impacts on the outcomes of IVF/ICSI with either fresh or frozen ET or on preimplantation embryo development and quality.

What are the fertility preservation rates of transgender women and transgender men, and what are the factors that affect their decision-making?This prospective study included 97 transgender women and 91 transgender men referred to the Gender Clinic of the study medical centre's Endocrinology Institute and to the Gan Meir Community Health Care Centre. The responders completed a 28-item questionnaire during 2018.Most of the transgender women and transgender men wished to parent a child (67.4% and 61.9%, respectively, P = 0.447), but only 40.4% of the transgender women and 5.8% of the transgender men used fertility preservation (P0.001). The main reasons for not pursuing fertility preservation were unwillingness to postpone gender-affirming treatment (58.8% and 74.0%, respectively, P = 0.076), preference to adopt a child (58.8% and 60.9%, respectively, P = 0.818) and cost (44.9% and 60.9%, respectively, P = 0.086). Factors related to the fertility preservation process itself were specifically chosen by transgender men compared with transgender women as the reason for not pursuing this treatment, including distress caused by the fertility preservation technique (60.3% versus 29.3%, respectively, P = 0.006), fear of gender dysphoria caused by hormonal treatment (63.5% versus 28.3%, P = 0.002) and concern over the attitude of medical staff (44% versus 19%, P = 0.027).Fertility preservation rates were considerably lower among transgender men than transgender women, strongly related to the fertility preservation process itself. Finding ways to overcome the obstacles confronted by transgender individuals, especially transgender men, will enhance their future biological parenting.

The purpose of this research is to study the efficacy of GnRH-a versus r-hCG triggering in patients who go through fertility preservation cycles. This retrospective cohort study was performed in a tertiary university-affiliated medical center. It includes 191 patients undergoing fertility preservation cycles between May 2013 and September 2018, in which ovulation was induced by either GnRH-a or r-hCG. Main outcome measures were number and rate of mature oocyte. Among treatment cycles with medical indication, GnRH agonist significantly increases the odds for high mature rate by 3.55 (1.30-9.66), while in treatment cycles with social indication, there is no significant effect of the triggering agent. An advantage for GnRH-a triggering was observed in medically indicated preservation cycles.

Background Data on who among the infertile male population may benefit from round spermatid injections (ROSI) are lacking. Objective To determine the probability of finding round spermatids suitable for ROSI in men with non-obstructive azoospermia (NOA) in whom no spermatozoa were retrieved at testicular sperm extraction. Materials and methods Four-hundred fifty-seven consecutive men with azoospermia underwent testicular sperm extraction. Clinical examination included age, secondary sexual characteristics, testicular size, reproductive hormone estimation, karyotyping, and Y chromosome microdeletion analyses. Histologic examination was performed, and histologic classification was determined by the most advanced spermatogenetic cell identified in the combined histologic and cytologic examination. Results Of the 457 azoospermic men, 342 were diagnosed with NOA, and 148 (148/342, 43%) had mixed atrophy on histopathology and retrievable spermatozoa. No spermatozoa were found in 194/342 men with NOA (57%). Histopathology diagnosed 145/194 (75%) of them with Sertoli cell only, 45/194 (23%) with spermatocyte maturation arrest, and 4/194 (2%) with spermatid maturation arrest. Conclusions Histopathologically identified round spermatids without spermatozoa were rare in men with NOA. Only very few of them are likely to reap the benefits of ROSI, thus presenting the need to reconsider its actual clinical value.

STUDY QUESTION Is the functional ovarian reserve in transgender men affected by testosterone therapy? SUMMARY ANSWER Serum anti-Müllerian Hormone (AMH) levels slightly decrease during testosterone treatment but remain within the normal range, suggesting preserved follicular ovarian reserve. WHAT IS KNOWN ALREADY Few small studies have investigated the impact of gender-affirming treatment on reproduction in transgender men. Conflicting results were reached concerning ovarian morphology and AMH levels in this context. STUDY DESIGN, SIZE, DURATION The study consisted of two arms. The first arm was a prospective pilot study, which enrolled 56 transgender men (median age 22.5 [interquartile range (IQR)—19–27.7] years), 27 of whom had polycystic ovary syndrome (PCOS), prior to the initiation of gender-affirming testosterone therapy. A structured assessment was conducted prior to, and at 3 and 12 months after treatment initiation. The second arm was a cross-sectional study that comprised 47 transgender men (median age 24 [IQR—20–31] years) who received testosterone for a median duration of 35 [IQR 13–62] months. The main outcome measures were serum AMH and antral follicle count (AFC) as indices of ovarian follicular reserve. PARTICIPANTS/MATERIALS, SETTING, METHODS The study was conducted at a tertiary center for transgender health. Gender-affirming therapy was administered according to standard practice. AFC was determined by pelvic (abdominal or transvaginal) ultrasound and blood collection for measurements of AMH, testosterone, estradiol, LH and FSH was performed at the designated time-points. MAIN RESULTS AND THE ROLE OF CHANCE Prospective arm for the entire group we observed a decrease of 0.71 ng/ml in AMH levels between baseline and 12 months (P = 0.01). When expressed in age-specific percentiles, AMH went from the 47.37th to the 40.25th percentile at 12 months (P LIMITATIONS, REASONS FOR CAUTION The limited sample size of the pilot study should be kept in mind. An additional limitation is the lack of a control group in the prospective study, as each participant served as his own control. Also, roughly 40% of the ultrasound examinations were performed transabdominally, potentially affecting the accuracy of the AFC measurements. As study participants were quite young, our reassuring data may not apply to older transgender men, either because of an age-related decline in ovarian reserve or to possible long-term effects of testosterone therapy. Furthermore, the chances for fertility preservation may be more limited in subjects with PCOS. WIDER IMPLICATIONS OF THE FINDINGS This is an additional contribution to the emerging evidence that prolonged testosterone treatment may not be a major obstacle to later fertility potential in transgender men desirous of having children. Larger confirmatory studies, and particularly more with reproductive outcome data, are needed for evidence-based fertility counseling prior to treatment initiation in these subjects. STUDY FUNDING/COMPETING INTEREST(S) This study received no funding. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER N/A.

The disposition decision is a frequently unresolved issue for many IVF users with surplus frozen embryos (SFEs), and this study draws attention to their experiences and moral work, locating it in the Jewish-Israeli context that legally enables the donation of SFEs to research but prohibits donation to other infertile people. To explore the (mis)understandings and (mis)communication underlying IVF users’ decisions concerning the fate of their SFEs, the records of 674 IVF users with SFEs stored for more than 5 years during 1996–2011 were analyzed, and 89 IVF users with different disposition decisions were recruited for semi-structured interviews. With an average of 5.1 SFEs, after an average of 8 years of storage, no response to a written request for a disposition decision came from 60% (n = 404) of IVF users with SFEs. Payment for storage and defrosting were the two most frequent choices (13%, n = 89 and 89, respectively) followed by donation to research and transfer (7%, n = 47 and 45, respectively). Three themes emerged from the interviews: misunderstanding the consequences of not returning the disposition form, communication gaps regarding donation to research, and the unmet wish to donate embryos to infertile people. We conclude by discussing the experiences and views of IVF users as reflecting the implications of the liminality and boundary-work surrounding the frozen embryo as a moral work object, and their consequences for policy recommendations.

A major challenge in clinical In-Vitro Fertilization (IVF) is selecting the highest quality embryo to transfer to the patient in the hopes of achieving a pregnancy. Time-lapse microscopy provides clinicians with a wealth of information for selecting embryos. However, the resulting movies of embryos are currently analyzed manually, which is time consuming and subjective. Here, we automate feature extraction of time-lapse microscopy of human embryos with a machine-learning pipeline of five convolutional neural networks (CNNs). Our pipeline consists of (1) semantic segmentation of the regions of the embryo, (2) regression predictions of fragment severity, (3) classification of the developmental stage, and object instance segmentation of (4) cells and (5) pronuclei. Our approach greatly speeds up the measurement of quantitative, biologically relevant features that may aid in embryo selection.

To compare clinical pregnancy rate (CPR) and live birth rate (LBR) after frozen-thawed embryo transfer (FET) of day (D-) 6 blastocysts on D-5 versus D-6. A retrospective cohort study. A university-affiliated single-center tertiary hospital. Women undergoing FET of D-6 blastocysts between August 2015 and March 2019 were included in the study. Exclusion criteria were endometriosis and maternal age ≥ 42. Cycles involving embryo transfer (ET) at D-6 were compared to cycles involving ET on D-5. Primary outcomes assessed were CPR and LBR, and the secondary outcomes were spontaneous abortion and chemical pregnancy rates. Forty-two cycles were assessed, 21 in which ET occurred on D-6 and 21 in which ET occurred on D-5. There were no significant differences between groups regarding age, body mass index (BMI), etiology of infertility, number of oocytes aspirated and blastocysts cryopreserved in the fresh cycle, reason for freezing on D-6, endometrial thickness before ET, and blastocyst grade. A comparison of outcomes of ET on D-5 with those involving ET on D-6 revealed that D-5 transfer produced significantly higher CPR (8, 38% vs. 2, 8.5%; P = 0.030) and LBR (6, 28.6% vs. 1, 4.8%; P = 0.038), respectively. FET of D-6 embryos on D-5 compared with D-6 is associated with increased CPR and LBR values. These findings might be related to the limited time window for optimal rates of implantation and indicate that transferring embryos on D-6 of a FET cycle is likely too late.

PURPOSE: To assess the effects of letrozole or tamoxifen coadministration on fertility preservation treatment outcomes. METHODS: Retrospective cohort study of 118 breast cancer patients undergoing fertility preservation treatment between 2008 and 2018. Patients who received letrozole (n = 36) or tamoxifen (n = 30) were compared to controls (n = 52) who underwent standard ovarian stimulation protocols. The primary outcome measures included the number of retrieved oocytes, mature oocytes (MII), fertilization, and top-quality embryo rates. The secondary outcome measures included duration of stimulation, gonadotropin dose and peak estradiol level. RESULTS: The number of oocytes retrieved, MII oocytes, fertilization rate, duration of stimulation, or gonadotropin dose were similar in the letrozole and tamoxifen groups, compared to controls. Top-quality embryo rate was lower in the tamoxifen group compared to controls (25% vs 39.4%, respectively, P = 0.034). The abnormal fertilization rate was higher in the letrozole group compared to controls (7.8% vs 3.60%, respectively, P = 0.015). A stepwise logistic regression analysis revealed that letrozole and peak estradiol were significantly associated with abnormal fertilization (OR 11.94; 95% CI 2.35–60.4, P = 0.003 for letrozole and OR 1.075; 95% CI 1.024–1.12, P = 0.004 per 100 unit change in estradiol). CONCLUSIONS: There may be a negative effect of letrozole or tamoxifen on fertilization and embryo quality, in fertility preservation cycles. Further studies are needed to confirm these findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-020-02030-y.

Women with inflammatory bowel disease (IBD) have an increased risk for adverse pregnancy outcome, so as women using assisted reproduction technology (ART). However, data are scarce regarding the risk imposed by the combination of both. Thus, we aimed to assess pregnancy outcome in these women.A retrospective case-control study, of women with IBD who conceived using ART due to female infertility. The study group (IBD-ART) was matched using propensity score and compared in a 1:1 ratio with three control groups, IBD patients who conceived spontaneously (IBD-SP), women using ART (H-ART) and women who conceived spontaneously (H-SP).The study group comprised of 49 women with IBD conceived via ART that gave birth at our center during the study period. All studied groups did not differ in demographics and obstetric characteristics. IBD groups (both ART and spontaneous) were comparable in disease status prior and throughout pregnancy. Maternal outcome showed no difference regarding preterm birth and pregnancy complications among all studied groups. Women in the IBD-ART group had decreased rates of vaginal delivery (34.7% vs 57.1%, p = 0.032) and higher rates of elective CS (32.7% vs 14.3%, p = 0.048) in comparison to H-SP group, but comparable rates to both IBD-SP and H-ART groups. Neonatal outcomes were comparable among all studied groups. In a sub-analysis by disease type, a higher rate of gestational diabetes was found among ulcerative colitis patients using ART (29.4% Crohn's vs 6.1% UC, p = 0.025).Patients with IBD undergoing ART have comparable pregnancy outcome to women using ART and to patients with IBD with spontaneous pregnancy.

Women of reproductive age with differentiated thyroid cancer (DTC) often need radioactive iodine (RAI) treatment after surgery. In contrast to the well-documented effect of RAI on testicular function, the potential negative effects of this treatment on ovarian reserve have been largely dismissed. The objective of this pilot study was to examine the possibility that RAI treatment is deleterious to the ovarian reserve by prospectively measuring the concentration of anti-Müllerian hormone (AMH) after RAI treatment.Thirty premenopausal women (MOf the 30 women, only 24 returned after the baseline assessment. RAI treatment resulted in a significant decrease in AMH concentrations at three months, from 3.25 ± 2.75 to 1.9 ± 1.74 ng/mL (p 0.0001). Only partial recovery was subsequently documented. Eighty-two percent of subjects had final values below baseline levels, such that at one year, serum AMH was still 32% lower than prior to treatment (2.36 ± 1.88 ng/mL; p 0.005). The only two continuous variables that correlated with the extent of AMH reduction at three months were the woman's age (r = 0.51; p = 0.02) and the age at menarche (r = 0.48; p = 0.03). Importantly, the RAI dose was not associated with the extent of AMH reduction and neither were smoking or the use of birth control pills. Older subjects (≥35 years) were significantly more likely to experience a marked AMH reduction at three months (63.7 ± 18.5% vs. 33.1 ± 29.2%; p = 0.01). The only predictor of recovery after one year was the extent of AMH decrease at three months: the lower the decline, the higher the chances for recovery.RAI in DTC has a rapid and profound effect on ovarian reserve, with only a partial recovery potential. In an era of declining human fertility, it is of relevance to recognize the potentially adverse effect of RAI in women of reproductive age. AMH measurement may be useful as a tool in this decision-making process.

PURPOSE: To compare fertility preservation (FP) outcomes among adolescent transgender males with those of cisgender females. METHODS: This retrospective cohort study included nine adolescent transgender males and 39 adolescent cisgender females who underwent FP between January 2017–April 2019 and September 2013–April 2019, respectively. The transgender males were referred before initiating testosterone, and the cisgender females were referred due to cancer diagnosis before starting anticancer treatment. Statistical analyses compared assisted reproductive technology (ART) data and FP outcomes between two groups. RESULTS: Basal FSH levels (5.4 ± 1.7 mIU/mL) and AFC (19.8 ± 5.6) of all transgender males were normal compared with standard references. The mean age of transgender males and cisgender females was similar (16.4 ± 1.1 vs 15.5 ± 1.3 years, respectively, P = 0.064). The amount of FSH used for stimulation was significantly lower among the former compared with the latter (2416 ± 1041 IU vs 4372 ± 1877 IU, P < 0.001), but the duration of stimulation was similar (12.6 ± 4.0 and 10.1 ± 2.8 days, P = 0.086). Peak estradiol level was significantly higher among transgender males compared with cisgender females (3073 ± 2637 pg/mL vs 1269 ± 975 pg/mL, respectively, P = 0.018), but there were no significant differences in number of retrieved oocytes between the two groups (30.6 ± 12.8 vs 22 ± 13.2, P = 0.091), number of MII oocytes (25.6 ± 12.9 vs 18.8 ± 11.2, P = 0.134), or maturity rates (81.5 ± 10.0% vs 85.4 ± 14.6%, P = 0.261). CONCLUSIONS: Adolescent transgender males have an excellent response to ovulation stimulation before initiating testosterone treatment. Oocyte cryopreservation is, therefore, a feasible and effective way for them to preserve their fertility for future biological parenting.

Objective To assess the effect of a sharp increase in estrogen levels on overactive bladder (OAB) symptoms among women undergoing ovulation induction. Methods 100 consecutive women (mean age 36.9 ± 5.2 years) who underwent IVF treatments, were prospectively enrolled. Three validated questionnaires on urinary urgency, urinary incontinence, and lower urinary tract symptoms were used to evaluate patient's OAB symptoms before ovulation induction (low estradiol level) and prior to ovum pickup (peak estradiol level). Results Of the 100 women, 49 reported OAB symptoms prior to ovulation induction (mean USIQ severity score 33) and 51 women were asymptomatic. Of the 49 symptomatic women, 44 (90%) remained symptomatic (mean USIQ severity score 34) and 5 women became asymptomatic through ovulation induction. Of the 51 asymptomatic women, 24 (47%) developed de novo OAB symptoms, while 27 women (53%) remained asymptomatic through ovulation induction. The mean peak estradiol level was significantly higher among women who remained asymptomatic in comparison to women with de novo OAB symptoms (2069 versus 1372 pg/ml; respectively). Moreover, in most (63%) women who remained asymptomatic, peak estradiol levels were higher than 1500 pg/ml, whereas in most (67%) women who became symptomatic, peak estradiol levels were lower than 1500 pg/ml. Conclusion A higher estradiol level appears to have a protective effect against the development of OAB symptoms during ovulation induction. Further, in most (63%) women who remained asymptomatic, peak estradiol levels were higher than 1500 pg/ml. This finding may suggest a threshold for estradiol activity in the lower urinary tract.

What is the fertility preservation rate among transgender women who have received professional fertility counselling compared with transgender men?This retrospective cohort study included 56 transgender women and 56 transgender men referred for comprehensive fertility counselling at the Gender Clinic of the Tel Aviv Sourasky Medical Center's Fertility Institute between January 2017 and April 2019. Statistical analyses were performed to compare transgender men with transgender women who preserved fertility and transgender people who preserved fertility and those that did not.The fertility preservation rate of transgender women was significantly higher than that of transgender men (85.7% versus 35.7%, respectively, P 0.001). The fertility preservation rate among transgender women was associated with being older and not having undergone gender-affirming hormone (GAH) treatment. The fertility preservation rate was higher among adolescent transgender boys compared with adolescent transgender girls (35% versus 6.25%, respectively, P = 0.005). The duration of GAH treatment among the transgender men who preserved fertility was 70 months compared with 18.6 months for transgender women (P = 0.05). All transgender boys opted for oocyte cryopreservation, while half of the transgender men who had not started GAH opted for oocyte cryopreservation, and half of those who had already started on GAH opted for embryo cryopreservation.High fertility preservation rates among transgender individuals were found after comprehensive fertility counselling. Fertility preservation rates among adults were higher among transgender women compared with transgender men, while the opposite was found in transgender adolescents.

Patients' preferences in choosing obstetricians/gynecologists are widely investigated, but studies among traditional populations are lacking. Bedouins comprise a traditional Arab Muslim society in the Arabian Peninsula (Saudi Arabia), The Levant (Syria, Jordan and Israel) and North Africa (Egypt). Most of the Bedouins in Israel populate several villages, mostly in the southern part of the country. This cross-sectional study compared 200 Bedouin and 200 Jewish women who responded to an anonymous questionnaire. Queried on gender alone, more Bedouin responders preferred female obstetricians/gynecologists (59.5 vs. 33% Jewish responders, p value

To determine the impact of pelvic inflammation caused by tubo-ovarian abscess (TOA) on ovarian response to stimulation. This retrospective longitudinal cohort analysis that was carried out in a tertiary university-affiliated medical center included 15 women with TOA during in vitro fertilization (IVF) cycles. The ovarian response to stimulation and the pregnancy rate were compared in two subsequent cycles, the initial IVF cycle that was complicated by TOA after oocyte retrieval (first treatment cycle) and the following IVF treatment (second treatment cycle) that occurred within a period of a year from the first cycle. The mean number of retrieved oocytes was significantly higher in the first IVF cycle compared to the second cycle (8.1 ± 3.2 vs. 5.4 ± 2.5, P = .003], corresponding to a 30% reduction in ovarian response to gonadotropin stimulation. Fertilization rates were significantly lower in the second cycle (4.1 ± 2.9 vs. 2.9 ± 1.7, P = .015). Twelve women (80%) reached embryo transfer in the first cycle compared to 14 women (93.3%) in the second cycle. The mean number of transferred embryos was similar between the two cycles. There were no clinical pregnancies following the first cycle, and only one patient (6.6%) had a clinical pregnancy in the second treatment cycle. TOA following fertility treatment has a detrimental effect on ovarian function. The pregnancy rate in the immediate period following TOA is poor. Current data for recommending the deferral of fertility treatment following a TOA episode are insufficient, calling for more studies to address these issues.

OBJECTIVE To investigate the developmental potential of oocytes and embryos derived from extremely small follicles (