Male Factor Infertility Research Articles

Abstract A042: History of infertility and risk of ovarian cancer in the women’s health initiative

Abstract Background: Given the consistent relationship between reproductive factors (e.g. parity) and risk of epithelial ovarian cancer, several studies have investigated the relation between infertility and ovarian cancer with conflicting results. Prior research has suggested differences in risk by specific infertility subgroups, which may have contributed to the conflicting findings. Further, few studies examined associations by ovarian cancer histotypes or were able to disentangle the influence of infertility vs. fertility treatment. Differences across studies could also have been influenced by different study populations (e.g., population-based vs. clinical population/registry of in-vitro fertilization [IVF]) and lack of consistent statistical control for important confounding factors including nulliparity, number of pregnancies, and age at first pregnancy. Finally, prior prospective studies have had limited follow-up, thus not capturing cancers that occur after menopause and which may have different risk factor profiles. Our objective was to determine the association between history of infertility and risk of postmenopausal ovarian cancer in a population that had not received treatment with IVF. Methods: We utilized the Women’s Health Initiative (n=114,761) with over 25 years of follow-up. At study baseline participants were asked whether they had ever tried to become pregnant for more than one year without becoming pregnant and whether a reason was found. Cox proportional hazards models were used to calculate the hazard ratios (HRs) of incident ovarian cancer comparing participants with a history of infertility to parous participants without infertility. Logistic regression models were used to calculate odds ratios (OR) for prevalent ovarian cancer at study baseline. Results: Approximately 16% of participants reported a history of infertility. 1,376 participants reported prevalent ovarian cancer at study baseline and 852 cases of ovarian cancer were diagnosed during study follow-up. In the prospective analyses, no statistically significant association was observed between infertility and risk of ovarian cancer overall (HR=1.16; 95% CI=0.98-1.37), by histotype, or with any specific infertility diagnoses. When prevalent ovarian cancer was examined, those reporting a history of infertility had a greater odds of ovarian cancer diagnosis (1.34; 95% CI=1.13-1.58) at WHI cohort baseline. This association was present for most infertility diagnoses with the strongest associations for hormonal/ovulatory (OR=1.97;95% CI=1.24-3.12), tubal/uterine factor (OR=1.63; 95% CI=1.15-2.31), and male factor (OR=1.71; 95% CI=1.19-2.47) infertility. Conclusions: We observed no significant association between infertility history and incident ovarian cancer in our population of postmenopausal participants. An association between infertility and ovarian cancer was present when prevalent ovarian cancer cases were examined, consistent with prior analyses that show stronger associations between ovarian cancer risk factors and ovarian cancer among younger women. Citation Format: Holly Harris, Kimberly Lind, Cynthia Thomson, Nazmus Saquib, Aladdin Shadyab, Peter Schnatz, Rogelio Robles-Morales, Lihong Qi, Howard Strickler, Denise Roe, Leslie Farland. History of infertility and risk of ovarian cancer in the women’s health initiative [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A042.

(271) Assessment of Varicocele Bilaterality in Infertile Men

Abstract Introduction Varicocele is the most common correctable cause of male factor infertility. It has always been a debatable subject as regard how it affects fertility and the best way to treat. However, there is a wide consensus nowadays that varicocelectomy improve male fertility potentials. Proper assessment of the disease bilaterality is crucial not to miss one side and not to jeopardize treatment outcome. Objective The primary outcome measure was to assess disease bilaterality and the secondary outcome measure was to report on improvement in semen 3 and 6 months post varicocelectomy and pregnancy rate 1 year post surgery. Methods This prospective study was conducted between January 2019 and January 2022. Infertile males with varicoceles underwent microsurgical subinguinal varicocelectomy by expert uroandrologists. Patients who were referred as unilateral varicoceles had their CDUS repeated for assessment of missed concomitant contralateral varicocele. Then, patients who were diagnosed with bilateral varicoceles underwent bilateral subinguinal ligation straight away. Those who were referred with unilateral varicocele had their palpable sides operated on first; then the contralateral side was also explored using an intraoperative Doppler device and the maximal vein diameter was measured. Patients came for follow for at least 6 months after surgery to evaluate any complications and assess improvement in semen parameters. Gynecologists also reported on normal pregnancy rate 1 year after surgery. Results A total of 329 cases completed the study. A hundred cases (30.4%) were initially referred as unilateral varicoceles and 229 (69.6%) as bilateral varicoceles. After reassessment of the study population, bilaterality of varicocele was found to be as high as 98.5% (324/329). This is statistically significantly higher than initial US (P<0.001). Repeat CDUS strongly correlated with the intraoperative measured varicocele diameter [r=0.9, P<0.001]. Moreover, sperm parameters showed significant improvement 3 and 6 months post varicocelectomy. Normal pregnancy after 1 year of surgery occurred in 118 cases (35.9%). Conclusions Varicocele bilaterality is underreported. Thorough assessment by expert radiologists and andrologists is of paramount importance not to miss significant pathology or hazard treatment outcome. Disclosure No.

Outcome of intrauterine insemination in couples with unexplained or male factor infertility at National Referral Hospital of Bhutan

Objectives: Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) is the only facility offering intrauterine insemination (IUI) services in the country. In this study, we aim to study the success rate of IUI for the year 2022. Material and Methods: This retrospective study utilized secondary data extracted from the medical records of a cohort of 57 patients who underwent IUI procedures at the infertility clinic between January and December 2022. Ethical clearance and site approval were obtained from the Institutional Review Board at Khesar Gyalpo University of Medical Sciences of Bhutan and JDWNRH, respectively. The Statistical Package for the Social Sciences version 26.0 by IBM Corp in Armonk, NY, was used to calculate frequencies, percentages and create statistical diagrams. Results: In the year 2022, the overall success rate of IUI was 5.3%. A majority of infertile men, representing 78.9%, fell within the age range of 30–39 years, and oligozoospermia emerged as the most common semen abnormality, affecting 45.6% of the infertile men in this study. Conclusion: Our study revealed that the IUI success rate in the country was 5.3%. This success rate of IUI in the country was found to be low compared to the success rate in neighboring countries. This is important information for patients to make informed decisions, aids fertility specialists in devising treatment plans, directs the allocation of resources, drives research and development initiatives, and informs policy and strategic adjustments at the national level.

Conventional in vitro fertilisation rather than intracytoplasmic sperm injection when only one oocyte is retrieved: Time to overcome irrational fears.

The use of intracytoplasmic sperm injection (ICSI) currently extends beyond male factor infertility, notably replacing conventional in vitro fertilisation (IVF) in scenarios like limited oocyte availability, where it is used as a precaution against complete fertilisation failure. While existing studies on the use of conventional IVF in such situations provide some reassurance, the available evidence is somewhat insufficient and ICSI is commonly used. To evaluate whether conventional IVF can be a feasible option when only one oocyte is retrieved. A retrospective study was performed to evaluate the fertilisation rate with conventional IVF in women retrieving only one oocyte and whose partner had normal semen. The study aimed at evaluating whether the fertilisation rate was aligned with the threshold indicated by recognized IVF laboratory performance indicators (Vienna Consensus). Clinical pregnancy and live birth rates were secondary outcomes. Out of 304 cycles with a single oocyte inseminated with conventional IVF, 209 achieved normal fertilisation and 82 did not. Thirteen had no mature oocytes. The fertilisation rate was 69% (95% CI: 63-74%) and increased to 72% (95% CI: 66-77%) when immature oocytes were excluded. The fertilisation rate surpassed the minimum competency threshold of the Vienna Consensus (60%), even if below the benchmark value (75%). Clinical pregnancy and live birth rates per oocyte retrieval were 10% and 8%, respectively. Univariate and multivariate analyses failed to identify any predictive factor of fertilisation. Conventional IVF with one oocyte met Vienna Consensus standards even if it fell short of higher benchmarks.

Deletion of ACTRT1 is associated with male infertility as sperm acrosomal ultrastructural defects and fertilization failure in human.

Could actin-related protein T1 (ACTRT1) deficiency be a potential pathogenic factor of human male infertility? A 110-kb microdeletion of the X chromosome, only including the ACTRT1 gene, was identified as responsible for infertility in two Chinese males with sperm showing acrosomal ultrastructural defects and fertilization failure. The actin-related proteins (e.g. ACTRT1, ACTRT2, ACTL7A, and ACTL9) interact with each other to form a multimeric complex in the subacrosomal region of spermatids, which is crucial for the acrosome-nucleus junction. Actrt1-knockout (KO) mice are severely subfertile owing to malformed sperm heads with detached acrosomes and partial fertilization failure. There are currently no reports on the association between ACTRT1 deletion and male infertility in humans. We recruited a cohort of 120 infertile males with sperm head deformations at a large tertiary hospital from August 2019 to August 2023. Genomic DNA extracted from the affected individuals underwent whole exome sequencing (WES), and in silico analyses were performed to identify genetic variants. Morphological analysis, functional assays, and ART were performed in 2022 and 2023. The ACTRT1 deficiency was identified by WES and confirmed by whole genome sequencing, PCR, and quantitative PCR. Genomic DNA of all family members was collected to define the hereditary mode. Papanicolaou staining and electronic microscopy were performed to reveal sperm morphological changes. Western blotting and immunostaining were performed to explore the pathological mechanism of ACTRT1 deficiency. ICSI combined with artificial oocyte activation (AOA) was applied for one proband. We identified a whole-gene deletion variant of ACTRT1 in two infertile males, which was inherited from their mothers, respectively. The probands exhibited sperm head deformations owing to acrosomal detachment, which is consistent with our previous observations on Actrt1-KO mice. Decreased expression and ectopic distribution of ACTL7A and phospholipase C zeta were observed in sperm samples from the probands. ICSI combined with AOA effectively solved the fertilization problem in Actrt1-KO mice and in one of the two probands. Additional cases are needed to further confirm the genetic contribution of ACTRT1 variants to male infertility. Our results reveal a gene-disease relation between the ACTRT1 deletion described here and human male infertility owing to acrosomal detachment and fertilization failure. This report also describes a good reproductive outcome of ART with ICSI-AOA for a proband. This work was supported by the Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau, 2023MSXM008 and 2023MSXM054). There are no competing interests to declare. N/A.

Sperm Preparation with Microfluidic Sperm Sorting Chip May Improve Intracytoplasmic Sperm Injection Outcomes Compared to Density Gradient Centrifugation.

Does sperm preparation using the FERTILE PLUS™ Sperm Sorting Chip improve fertilization rates, blastocyst formation, utilization, and euploidy rates in patients undergoing intracytoplasmic sperm injection (ICSI), compared with density gradient centrifugation (DGC)? A single-cohort, retrospective data review including data from 53 couples who underwent ICSI cycles within a 12-month period. For each couple, the two closest, consecutive cycles were identified, where one used the standard technique of sperm preparation (DGC) and the subsequent used FERTILE PLUS™, therefore, couples acted as their own controls. Paired samples t-test was used to compare means for the outcomes (fertilization, blastocyst formation, utilization, and euploidy rates). Binary logistic regression analysis assessed the relationship between female age, the presence of male factor infertility, and euploidy rates. Blastocyst, utilization, and euploidy rates were significantly higher for cycles using FERTILE PLUS™ compared to DGC (76% vs 56%, p = 0.002; 60% vs 41%, p = 0.005, and 40% vs 20%, p = 0.001, respectively). Although there was an increase in fertilization rates for cycles using FERTILE PLUS™, this was not significant (72% vs 68%, p = 0.449). The euploidy rates of females ≤ 35 years were significantly increased when the FERTILE PLUS™ sperm preparation method was used, compared to the older age group (OR 2.31, p = 0.007). No significant association was found between the presence or absence of male factor infertility and euploidy rates between the two cycles. This study provides tentative evidence that the FERTILE PLUS™ microfluidic sorting device for sperm selection can improve blastocyst formation, utilization, and euploidy rates following ICSI in comparison to the DGC method.

Reassessing the impact of letrozole co-administration in controlled ovarian hyperstimulation: findings from a single-center repeated measures study.

To explore whether letrozole improved outcomes in subsequent controlled ovarian hyperstimulation (COH) cycles. This was a retrospective repeated measures cohort study examining COH cycles. Patients were included if they underwent two cycles for unexplained infertility, male factor infertility, or planned oocyte/embryo cryopreservation. The first cycles for all patients implemented a non-letrozole, conventional gonadotropin protocol. Second cycles for the study group included letrozole (2.5-7.5 mg for 5 days) with no medication change to second cycles amongst controls. Our primary objective was to compare oocyte yield. Cohorts were then subdivided by pursuit of oocyte (OC) or embryo (IVF) cryopreservation. Secondary outcome amongst the OC subgroup was oocyte maturation index (metaphase II (MII)/total oocytes). Secondary outcomes amongst the IVF subgroup were normal fertilization rate (2-pronuclear zygotes (2PN)/oocytes exposed to sperm), blastocyst formation rate (blastocysts/2PNs), and embryo ploidy (%euploid and aneuploid). Fifty-four cycles (n = 27) were included in letrozole and 108 cycles (n = 54) were included in control. Oocyte yield was higher in second cycles (p < 0.008) in the letrozole group but similar in second cycles (p = 0.26) amongst controls. Addition of letrozole did not impact MII index (p = 0.90); however, MII index improved in second cycles amongst controls (p < 0.001). Both groups had similar rates of normal fertilization (letrozole: p = 0.52; control: p = 0.61), blast formation (letrozole: p = 0.61; control: p = 0.84), euploid (letrozole: p = 0.29; control: p = 0.47), and aneuploid embryos (letrozole: p = 0.17; control: p = 0.78) between cycles. Despite improved oocyte yield, letrozole did not yield any difference in oocyte maturation or embryo outcomes.

The psychosocial impact of male infertility on men undergoing ICSI treatment: a qualitative study.

Male infertility is in 20-70% of cases the cause of a couple's infertility. Severe forms of male infertility are best treated with Intracytoplasmic Sperm Injection (ICSI). The psychosocial impact of infertility and ICSI on men is unclear because the focus is socially, clinically, and scientifically on women. However, there is evidence that it can affect the psychological well-being of men, but these studies are mainly quantitative. Qualitative research needed to explore the experiences of infertile men in-depth is limited. Therefore, the objective of this study was to clarify the psychosocial consequences of male infertility on men undergoing ICSI to understand their experiences with reproduction problems more comprehensively. In this generic qualitative study, men who were undergoing or had undergone ICSI after a male factor infertility diagnosis were included. A purposive sample with maximum variation was sought in a fertility clinic of one university medical centre in the Netherlands. Data were collected through individual face-to-face semi-structured interviews. Thematic analysis was used to identify themes from the data. Nineteen Dutch men were interviewed. The mean duration of the interviews was 90min. An everyday contributing backpack was identified as the main theme, as men indicated that they always carried the psychosocial consequences of infertility and ICSI with them. Different world perspective, Turbulence of emotions, Changing relation, and Selective sharing were the psychosocial consequences that men were most affected by. Moreover, men indicated that they were Searching for contribution during ICSI because the focus was entirely on the woman. Men with male infertility experience psychosocial problems due to infertility and ICSI treatment. Healthcare professionals need to recognize the impact of infertility on men and create room for a role for them during ICSI.

A RETROSPECTIVE STUDY ON MATERNAL AND FETAL OUTCOMES ASSOCIATED WITH ASSISTED REPRODUCTIVE TECHNOLOGIES

Assisted Reproductive Technologies (ART) have revolutionized the landscape of reproductive medicine, offering hope to couples facing infertility challenges. The study's main objective is to find the maternal and fetal outcomes associated with assisted reproductive technologies. This retrospective cohort study was conducted in Lady Reading Hospital Peshawar from July 2019 to June 2023. The study includes 850 participants who underwent ART procedures between 2021 and 2022. Details of the ART procedures, such as the technique employed, the number of embryos transferred, and the utilization of preimplantation genetic testing, were meticulously documented. Maternal outcomes were a focal point, with a comprehensive assessment of pregnancy-related hypertensive disorders, gestational diabetes, mode of delivery, and any postpartum complications. Data was collected from 850 participants. The mean maternal age was 33.5 years (SD = 4.2), and the mean BMI was 25.8 (SD = 3.5). The primary causes of infertility varied, with male factor infertility being the most prevalent at 40%, followed by ovulatory dysfunction at 30% and unexplained infertility at 20%. The ART procedures in the study cohort comprised In Vitro Fertilization (IVF) at 60%, followed by Intracytoplasmic Sperm Injection (ICSI) at 25%, and other ART techniques at 15%. Regarding the number of embryos transferred, the majority received a single source (70%), with 20% receiving two starts and 10% receiving three or more. It is concluded that pregnancies conceived through Assisted Reproductive Technologies (ART) exhibit a higher prevalence of pregnancy-related hypertensive disorders and gestational diabetes compared to naturally conceived pregnancies.

Assessment of clinical pregnancies in up to eight ovarian stimulation with intrauterine insemination treatment cycles in those unable to proceed with in vitro fertilization

To study the primary objective of clinical pregnancy (CP) rate per ovarian stimulation with intrauterine insemination (OS-IUI) treatment cycle in patients with repetitive cycles up to a maximum of 8 cycles. Retrospective cohort. Large fertility clinic. A total of 37,565 consecutive OS-IUI cycles from 18,509 patients were included in this study. Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. The CP rate was analyzed using generalized estimating equations and controlled for age, stimulation protocol, and body mass index. Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. A total of 37,565 consecutive OS-IUI cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients aged <35 years comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of CP for cycles one to 8 was 15.7% per cycle. The mean predicted probability of CP in aggregated data from cycles 2 to 4 was only 1.7% lower compared with cycle 1 as the referent (16.7% vs. 15.0%, 95% confidence interval [CI] 2nd: 0.88 {0.82, 0.95}, 3rd: 0.86 {0.79, 0.93}, 4th: 0.88 {0.79, 0.98}). However, the 15.0% mean predicted probability of CP for the second through the fourth cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of CP of cycles 5 to 8 was not significantly different compared with the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 [0.85, 1.11], 6th: 0.93 [0.79, 1.10], 7th: 1.01 [0.81, 1.26], 8th: 1.01 [0.76, 1.34]). The modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of CP from OS-IUI continues to increase with each of the 8 successive cycles. Clinical pregnancy rates are satisfactory in up to 8 consecutive OS-IUI treatment cycles. These data are useful for counseling, especially in those patients for whom invitro fertilization is not financially or ethically feasible.

The impact of microfluidics sperm processing on blastocyst euploidy rates compared with density gradient centrifugation: a sibling oocyte double-blinded prospective randomized clinical trial

ObjectiveTo compare euploidy rates among blastocysts created from sibling oocytes injected with sperm processed by microfluidics or by density gradient centrifugation. DesignSibling oocyte randomized controlled trial. SettingSingle university-affiliated infertility practice. Patient(s)106 patients aged 18-42 undergoing fresh in vitro fertilization (IVF) cycles with preimplantation genetic testing (PGT) between January 2021 to April 2022 contributed 1442 mature oocytes which were injected with sperm processed via microfluidics or density gradient centrifugation. Intervention(s)Sperm sample divided and processed via a microfluidics device and density gradient centrifugation for injection into sibling oocytes. Main outcome measure(s)Primary outcome was the embryo euploidy rate. Secondary outcomes included the fertilization, high quality blastulation, and ongoing pregnancy rates. Result(s)The blastocyst euploidy rate per mature oocyte was not significantly different in the study group compared to the control group (22.9% versus 20.5%, p = 0.60). The blastocyst euploidy rate per biopsied embryo was also similar between the two groups (53.0% versus 45.7%, p = 0.34). However, the fertilization rate per mature oocyte injected was found to be significantly higher in the study group compared to the control group (76.0% versus 69.9%, p = 0.03). The high quality blastulation rate per mature oocyte injected was similar between the two groups, as was the total number of embryos frozen. There were no differences in the number of participants with no blastocysts for biopsy or the number of participants with no euploid embryos between the two groups. Among the male factor infertility and recurrent pregnancy loss subgroups, there were no differences in euploidy rates, fertilization rates, blastulation rates, or total numbers of blastocysts frozen, although the study was underpowered to detect these differences. Seventy-seven patients underwent frozen embryo transfer; there were no significant differences in pregnancy outcomes between the two groups. Conclusion(s)Microfluidics processing did not improve embryo euploidy rates compared to density gradient centrifugation in this sibling oocyte study, although fertilization rates were significantly higher.

The effect of laser-assisted hatching on vitrified/warmed blastocysts: the ALADDIN randomized controlled trial

ObjectiveTo evaluate whether laser-mediated assisted hatching (AH) performed on vitrified/warmed blastocysts before embryo transfer can improve live birth rate. DesignThe “pArtiaL zonA pelluciDa removal by assisteD hatchINg of blastocysts (ALADDIN)” is a 2-center comparative study with a parallel randomized controlled design. SubjectsParticipants were recruited between September 2018 and November 2021. They were aged 18 to 39 years, underwent non-donor IVF cycles, and were scheduled for elective single embryo transfer with vitrified/warmed blastocysts. Those with uterine abnormalities, BMI >35 kg/m2, severe male factor infertility, or performing preimplantation genetic testing were excluded. InterventionAssisted hatching was performed using a 1480 nm diode laser, removing approximately one-third of the zona pellucida with continuous 0.2 ms pulses applied from the 1 to 5 o’clock positions. Main Outcome MeasuresThe primary outcome was the live birth rate. Secondary endpoints included clinical pregnancy, miscarriage, multiple pregnancies, preterm births, obstetrical and neonatal complications, and congenital anomalies. ResultsOverall, 698 participants met the inclusion criteria and were randomized: 352 patients were assigned to the AH arm and 346 to the control arm. One-hundred and five (29.8%) and 101 (29.2%) participants achieved a live birth following treatment, respectively (p=0.87). The relative risk of live birth in patients with vitrified/warmed blastocysts treated with AH was 1.02 (95%CI: 0.86-1.19). Exploratory subgroup analyses for women’s age, recruiting centers, indications for IVF, method of insemination, blastocyst quality, and days of blastocyst development failed to highlight any clinical situation that could benefit from AH in thawed blastocysts. ConclusionIn patients undergoing frozen embryo transfer with vitrified/warmed blastocysts, laser AH does not improve the live birth rate. Further studies are required to rule out milder but potentially interesting benefits in specific subgroups of patients.

Hyaluronan Sperm Selection during ICSI (HA-ICSI) Increases Embryo Utilization in Couples with Male Factor Infertility

Background: Hyaluronan (HA) sperm selection, utilizing the affinity of mature sperm for HA, has emerged as a technique to enhance the selection of sperm for intracytoplasmic sperm injection (ICSI). However, conflicting evidence exists regarding the impact of HA-ICSI on clinical outcomes including fertilization, embryo utilization, and pregnancy rates. The study aimed to compare clinical outcomes including fertilization, utilization, and pregnancy rates between paired ICSI and HA-ICSI cycles within patients, particularly for male factor and low utilization subgroups. Methods: A retrospective study from 3,988 ICSI treatment cycles was conducted between January 2018 and March 2022. A HA-ICSI cycle was paired with the preceding ICSI cycle from the same patient. Fertilization, utilization, and clinical pregnancy rates were compared based on infertility diagnosis and utilization rate (UR) from the initial ICSI cycle. Results: There were no differences in fertilization, utilization, embryo quality, euploidy, or pregnancy rates between ICSI and HA-ICSI in all paired cycles. However, for patients with male factor infertility UR increased from 25.0% to 38.5% in their HA-ICSI cycle ([Formula: see text]). There was no difference observed for female factor infertility patients. HA-ICSI use was of particular benefit for male factor infertility patients with low ([Formula: see text]) embryo utilization in their initial ICSI cycle, evident by an increased utilization from 14.3% to 25.0% in their HA cycle ([Formula: see text]). Conclusions: This is the first study to focus on the impact of HA-ICSI on embryo utilization, particularly in patients with male factor infertility. The efficacy of HA-ICSI as a sperm selection tool appears to be limited to improving UR in patients with male factor infertility, particularly those with low utilization in a previous ICSI cycle, with no significant effect on fertilization or pregnancy rates. Conclusion: HA-ICSI may be useful for sperm selection at the time of ICSI for a select subgroup of patients. Male factor infertility patients, who have previously undertaken an ICSI cycle with less than 40% utilization, should be considered as candidates for treatment.

(303) The Predictive Role of Baseline Hormone Profile Evaluation for the Likelihood of Having a Child in Infertile Men

Abstract Introduction Sex hormone profile evaluation is commonly used in male infertility assessment to identify potential hormonal imbalances and underlying issues that can impact sperm production, sperm quality, or reproductive organ function. Objective To evaluate the likelihood of having a child in subfertile and infertile men within five years based on their serum hormone levels on their initial encounter for infertility evaluation/treatment. Methods We identified a retrospective cohort from the Subfertility, Health, and Assisted Reproduction (SHARE) study (compiled 1996-2017) linked with familial information from the Utah Population Database (UPDB) including all men with a measured value of albumin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Free testosterone (T), total, and bioavailable T, sex hormone binding globulin (SHBG), and estradiol (E). We included men who had a semen analysis (SA) within 1 year of their hormone measurement. The primary outcome of the study was any evidence of childbirth, and the secondary outcome was the time from baseline hormone evaluation to childbirth. All men were followed for 60 months after their recorded hormone value for evidence of childbirth. Using Cox proportional hazards models, we modeled the likelihood of having a child and the time to childbirth (using linear regression) against the quintile of hormone distribution. Results A total number of 1298 men who underwent hormone profile evaluation and SA were included in this study. The mean age for the total cohort was 33 (29-37) years old. Men who had a child at the end of the study period (31 (28-36)) were significantly younger than men without a child at the end of the study with a mean age of (35.5 (32-40.25)) (p &amp;lt; 0.001). The mean sperm concentration for the total cohort was 7.6 (1-27.4) (M/ml) and the mean total progressive motile count was 9 (0.9-47) (M). Overall, semen parameters showed no significant differences between men who had a child at the end of the study follow-up versus men who did not. Our models showed that prolactin serum levels in quantile 7 have the highest ratio (2.236 (0.919-5.44) p=0.076) for the likelihood of having a child. Total testosterone in quantiles 3 and 5 showed an increased likelihood of having a child (2.119 (1.176-3.821) (p=0.012), (2.518 (1.412-4.491)) (p=0.002), respectively. Albumin in quantiles 5-9 followed a similar pattern with the highest ratio in quantile 8 (3.551 (1.486-8.487)) (p=0.004). Our results did not show meaningful patterns between semen parameters, serum hormone levels, and time to having a child. Conclusions The outcomes of this study indicate that prolactin, total testosterone, and albumin serum levels on the first visit in men with infertility concerns are associated with an increased likelihood of having a child. Abnormal semen analysis outcomes are not well associated with hypoandrogenism in infertile men. Our study shows that baseline serum prolactin, total testosterone, and albumin levels can be used to estimate the likelihood of having a child in subfertile and infertile men. These findings can provide the basis for further studies to determine an optimal screening method for male-factor infertility related to abnormal hormone levels. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Equity/salary/officer in company: Paterna bio, firmtech; Consulting: Turtle health, maximus, carrot; inherent bio.

Fertility counselling and fertility preservation among early onset female cancer patients-A Finnish register-based study.

Advances in multimodality cancer treatments have increased long-term survival rates for early onset cancer patients, with 5-year survival rates reaching 80% in Northern Europe. According to recent recommendations, clinicians should, as early as possible, inform cancer patients about the impact that cancer treatment may have on their fertility. Still, there is limited published data on fertility counselling (FC) and fertility preservation (FP) for cancer patients. This register-based study used hospital records to identify female cancer patients in the hospital district (n = 192) who received FC at the age of 16-42 years between 2011 and 2019. Altogether, 97 (50.5%) cancer patients were eligible for FP. Of these, 55 (56.7%) underwent FP, whereas 42 (43.3%) declined. Women undergoing FP were recommended cancer treatments with a higher risk of infertility (p = 0.01), and women with breast cancer were more prone to undergo FP than women with lymphoma (p = 0.043). In FP treatment cycles, the mean number of oocytes retrieved (13.9 ± 7.7 vs. 12.0 ± 6.5, p = 0.04) and transferrable embryos (4.7 ± 2.9 vs. 3.7 ± 2.8, p = 0.002) was higher among cancer patients compared to age-matched comparisons with male or tubal factor infertility. The total mean gonadotropin dose used was higher among cancer patients (2243 ± 963 IU vs. 1679 ± 765 IU, p < 0.001). We conclude that a good ovarian response during FP can be achieved in female cancer patients.

The Evolving Landscape of Male Varicocele Pathophysiology in the Era of Multi-Omics: A Narrative Review of the Current Literature.

Male-factor infertility is implicated in over half of the millions of cases of infertility worldwide, and varicoceles are the most common correctable cause of male-factor infertility. The pathophysiologic mechanism for varicoceles is complex and next-generation technologies offer promising insights into the molecular underpinnings of this condition. In this narrative review, we highlight historical and contemporary paradigms associated with varicoceles, with an emphasis on the biological underpinnings of this disease. Specifically, we review the literature describing the underlying causes of varicoceles, discuss the molecular and cellular mechanisms causing pathological changes in some (but not all) men, and highlight key articles regarding the next-generation analyses (e.g., transcriptome, epigenome, proteome, and microbiome) being applied to better understand the condition and its treatment. These data demonstrate an ongoing evolution of the knowledge of varicoceles and the potential for improved personalized care in the future for men with this condition.

Evaluation of telomere length, reactive oxygen species, and apoptosis in spermatozoa of patients with oligospermia.

50% of cases of infertility are caused by male factor, which acquired or congenital problems may bring on. Male infertility can be caused by oligospermia and asthenozoospermia, which are common. Since the same mutations that cause azoospermia in some people also cause oligozoospermia in others, oligozoospermia may be thought of as a less severe form of azoospermia. Studies have demonstrated telomere length, catalase activity, super oxide dismutase (SOD), and DNA fragmentation can be influential factors for male infertility. The amount of apoptosis, oxidative stress factors, telomere length, and DNA fragmentation were some aspects of healthy sperm that we chose to look into in this study and compare to oligospermia individuals. Oligospermia patients (n = 24) and fertile men (n = 27) semen samples were collected, and the apoptosis rate of sperms in both groups was analyzed (Flow cytometry). Also, gene expression of apoptotic and antiapoptotic markers and telomere length were examined (real-time polymerase chain reaction). The sperm DNA fragmentation kit was used to determine DNA fragmentation and to evaluate catalase and SOD activity; the specific kits and methods were utilized. Higher expression levels of caspase3 (p = .0042), caspase8 (p = .0145), caspase9 (p = .0275), and BAX (p = .0202) mRNA were observed in patients who had oligospermia. In contrast, lower mRNA expression of BCL-2 (p = .0009) was detected in this group. In addition, telomere length was decreased in the oligospermia group (p < .0001) compared to the health group. Moreover, the frequency of apoptosis is induced in patients (p = .0026). The catalase activity is low (p = .0008), but the SOD activity is high (p = .0015) in the patient group. As a result of our findings, we may list the sperm cell apoptosis rate, telomere length, the degree of sperm DNA fragmentation, and lastly, the measurement of significant and efficient oxidative stress markers like SOD and catalase in semen plasma among the principal diagnostic characteristics for oligospermia. Future studies will be better able to treat oligospermia by showing whether these indicators are rising or falling.

Prevalence and predictors of ovarian hyper stimulation syndrome at Center fertility and repro-ductive medicine at Public IVF center, Ethiopia

Abstract Background Infertility affects fifteen percent of couples who wish to conceive. The mainstay of artificial reproductive technologies is in vitro fertilization and embryo transfer (IVF-ET), in which aspirated Oocytes are fertilized, followed by the trans cervical replacement of an embryo(s) into the uterine cavity.However, the practice of assisted reproductive technology is loaded with short- and long-term complications. Complications may occur during the course of stimulation, ovum pickup, or embryo transfer. Ample studies are done on in vitro fertilization, but the frequency and importance of complications of IVF in low-resource setups where the treatment itself is not widely available are poorly known. Objective This study aimed to determine the rate of ovarian hyper stimulation syndrome and associated factors among women who underwent controlled ovarian stimulation and IVF in a public IVF center. Methodology A simple random sampling technique was used to review the medical records of women who have undergone ovarian stimulation and IVF treatment at the Saint Paul’s Hospital Center for Reproductive Medicine and IVF. Results A total of 428 clients had controlled ovarian stimulation and IVF. The mean age of the participants was33yrs among 428 couples who had IVF, majority 245 (57%) had IVF for female factor infertility followed by male factor infertility 89(20%) and unexplained causes 53(12%). The incidence of OHSS in our IVF population was 19(4.4%) out of 428 women. out of the 22 patients with OHSS 17 (87%) developed mild and moderate and the rest 2 out of 22(10 %) had severe OHSS. The odd of developing OHSS was 6 times among those with PCOS, OR 5.78 CI (1.19, 28.22), p value of 0.03. Conclusions and recommendations The overall rate of ovarian hyper stimulation syndrome is higher in our IVF population. Emphasis should be given on counseling and risk minimizing measures when women withPCOS Key words: IVF, Complications, Ovarian hyperstimulation syndrome

Associations of legacy perfluoroalkyl and polyfluoroalkyl substances, alternatives, and isomers with gestational diabetes mellitus and glucose homeostasis among women conceiving through assisted reproduction in Shanghai, China.

Prior research has reported that perfluoroalkyl and polyfluoroalkyl substances (PFAS) may be linked to impaired glucose homeostasis in pregnant women. However, few studies have investigated PFAS alternatives and isomers, and even less is known about the association among women conceiving through assisted reproductive technology (ART). The prospective cohort study aimed to explore associations of legacy PFAS, alternatives and isomers with gestational diabetes mellitus (GDM) and glucose homeostasis during pregnancy among 336 women conceiving through ART. Nineteen PFAS, including nine linear legacy PFAS, four short-chain alternatives, four branched isomers, and two emerging PFAS alternatives, were determined in first-trimester maternal serum. Fasting plasma glucose (FPG), 1-h and 2-h glucose concentrations following the oral glucose tolerance test (OGTT), and glycated hemoglobin (HbA1c) were measured during the second trimester. After adjusting for confounding variables, nearly half of individual PFAS (10/19) and PFAS mixtures were correlated with increased GDM risk or elevated 2-h glucose levels. Among PFAS congeners, emerging PFAS alternatives, chlorinated perfluoroalkyl ether sulfonic acids (Cl-PFESAs), showed a notable association with impaired glucose homeostasis. For example, 6:2 Cl-PFESA exhibited a correlation with GDM (OR = 1.31, 95% CI = 1.02, 1.68) and 2-h glucose concentrations (β = 0.22, 95% CI = 0.08, 0.36), and contributed most to the overall association with 2-h glucose concentrations. Compared to those diagnosed with male factor infertility, the associations were more pronounced in infertile women with reproductive endocrine diseases. We provide evidence that exposure to PFAS, especially emerging PFAS alternatives, may impair glucose homeostasis and increase the risk of GDM among women conceiving through ART.

Discriminatory Value of Steroid Hormones on Polycystic Ovary Syndrome and Clustering of Hyperandrogenism and Metabolic Factors

ObjectiveWe determined (1) if 11-oxygenated androgens better identify polycystic ovary syndrome (PCOS) diagnosis in women with obesity compared to total or free testosterone (T) and free androgen index; (2) how biochemical hyperandrogenism and metabolic factors cluster in a cohort of women with infertility and obesity. MethodsWomen with obesity and PCOS comprised the study group (N = 132). Ovulatory women with obesity and idiopathic, tubal or male factor infertility were the control group (N = 83). Steroid hormones were measured by means of liquid chromatography tandem mass spectrometry. Receiver operating characteristic curves and principal component analysis were used. ResultsWomen with obesity and PCOS had higher 11-ketotestosterone (11 KT) (1.22 nmol/L [0.84; 1.65] vs 1.05 [0.78; 1.35], P = .04) compared to controls, but not 11β-hydroxyandrostenedione 4.30 [2.87; 5.92] vs 4.06 [3.22; 5.73], P = .44). 11-ketotestosterone (area under the curve: 0.59) did not better discriminate PCOS in women with obesity compared to: total T (0.84), free T (0.91), and free androgen index (0.85). We identified 4 principal components (PCs) in the PCOS group (72.1% explained variance): (1) insulin resistance status; (2) blood pressure; (3) obesity; (4) androgen status and 4 PCs in the control group (68.7% explained variance) with variables representing metabolism being dispersed in component 2, 3, and 4. ConclusionsEleven-oxygenated androgens do not aid in the diagnosis of PCOS in women with obesity. Insulin resistance is the strongest PC in the PCOS group. There is no major dominant characteristic that defines obese non-PCOS women.