Fertility Center Research Articles

Best Washing Method for Oligoasthenospermic Patients by Evaluating DNA Integrity by using Comet Assay Study

Background: Sperm is more than just a mere transporter of paternal genetic information, although serving purposes other than conception. DNA integrity (DI) is regarded as a crucial aspect of semen quality and has great significance in predicting male fertility. Washing sperm is a form of preparation of sperm which is essential before processing intra-uterine-insemination since it removes chemicals from semen that might cause adversarial reactions in the uterus. During the process of washing, sperm gets separated from seminal fluid, which gradually improves the fertilizing capability of sperm, and numerous existing methods have faced complications with the determination of effective integrity in washing methods. The objective of the present study was to find the DI of the sperms through three washing methods that, include the density gradient (DG) method, swim up (SU) method, and magnetically activated cell sorting (MACS) method after the cryo-preservation (CP) for 3 months. Methodology: Semen samples were obtained from 40 oligoasthenospermic patients with progressive motility <32%, who underwent assisted reproductive technology procedure in Sumathi fertility center in Madurai between October 2021 and December 2021. Sperm washing is performed through three different mentioned techniques. The grades of the comet reflected five different classes from class 0 to class 4. These data were analyzed using one-way ANOVA test, and multiple comparisons were performed between these groups using Tukey’s test. Results: The results showed a high level of normal sperm (68%) in the DG method than the SU (47%) and MACS (42%) sperm preparation techniques that specified by significant elevation (P < 0.001) of class 0 comet tails. Conclusion: It was observed that the DG method has the best and success rates for intracytoplasmic sperm injection and in vitro fertilization was relatively high.

Spiritual Coping and Quality of Life in Infertile Couples: Evidence from a Fertility Center in Lahore, Pakistan

This study aims to investigate the association between spiritual coping and quality of life in infertile couples. The researchers used a cross-sectional survey research design for carrying out this study. Data was collected from 58 infertile couples visiting Lahore Institute of Fertility and Endocrinology (LIFE), Hameed Latif Hospital for infertility diagnosis or treatment. A self-structured questionnaire was used to collect data about socio-demographics, spiritual coping and quality of life. The researchers used SPSS IBM Version 21.0 to analyze quantitative data. The results showed a significant relationship between spiritual coping and quality of life in infertile couples. It was furthermore found that spiritual coping and quality of life in infertile couples varied across their gender, age, education, area of residence, family system and income level. On the basis of these findings, the researchers suggest that infertility counseling should be imparted at fertility centers involving spiritual coping that may help infertile couples in improving their quality of life, especially during the treatment process.

Complex factors related to marital and sexual satisfaction among couples undergoing infertility treatment: A cross-sectional study

ObjectivesThis study assesses complex factors related to marital and sexual satisfaction among couples undergoing infertility treatment. MethodsThis cross-sectional study was conducted with 140 couples who visited fertility centers in Iran, between September 2015 and July 2016. Data collection was done by Marital and Sexual Satisfaction Questionnaires and were analyzed by the IBM SPSS 26 software. ResultsThere was a significant difference between wives and husbands in the MSQ total scores (p = 0.027). However, there was no significant difference between wives and husbands in the SSQ total scores (p = 0.398). Sexual satisfaction and decision-maker in life among wives and husbands were significant predictors of MSQ. The kind of treatment, cause of infertility and BMI among wives and kinds of treatment, cause of infertility, and decision-maker among husbands were also significant predictors of SSQ. ConclusionThe findings of this study showed that there is a difference between the understanding of marital and sexual satisfaction in wives and their husbands. Healthcare providers need to pay more attention to these differences.

Identification of common genetic polymorphisms associated with down-regulated gonadotropin levels in an exome-wide association study

To investigate whether common genetic polymorphisms are associated with gonadotropin levels after down-regulation with daily gonadotropin-releasing hormone agonist and whether the polymorphisms of candidate variants influence the ovarian response to exogenous gonadotropins. Genetic association study. University-affiliated invitro fertilization center. Subjects enrolled in an exploratory exome-wide association study (n = 862), a replication exome-wide association study (n= 86), and a classifier validation study (n = 148) were recruited from September 2016 to October 2018, September 2019 to September 2020, and January 2021 to December 2021, respectively. The included patients were aged ≤40 years and had a basal follicle-stimulating hormone (FSH) ≤12 IU/L. All participants received a luteal phase down-regulation long protocol. Genome DNA was extracted from the peripheral blood leukocytes. For the exploratory and replication cohorts, exome sequencing was conducted on a HiSeq 2500 sequencing platform. The multiplex polymerase chain reaction amplification technique and next-generation sequencing also were performed in the exploratory and replication cohorts. For the samples of the validation cohort, Sanger sequencing was performed. The primary endpoint was the gonadotropin levels after down-regulation, and the secondary endpoints were hormone levels and follicle diameters during stimulation, the total dose of FSH, duration of FSH stimulation, number of oocytes retrieved, and clinical pregnancy rate. In the exploratory cohort, we identified that FSHB rs6169 (P=2.71 × 10-24) and its single-nucleotide polymorphisms in high linkage disequilibrium were associated with the down-regulated FSH level. The same locus was confirmed in the replication cohort. Women carrying the C allele of FSHB rs6169 exhibited higher average estradiol level during stimulation (P=6.82 × 10-5), shorter duration of stimulation, and less amount of exogenous FSH (Pduration=0.0002; Pdose=0.0024). In the independent validation set, adding rs6169 genotypes into the prediction model for FSH level after down-regulation enhanced the area under the curve from 0.560 to 0.712 in a logistic regression model, and increased prediction accuracy by 41.05% when a support vector machine classifier was applied. The C allele of FSHB rs6169 is a susceptibility site for the relatively high level of FSH after down-regulation, which may be associated with increased ovarian FSH sensitivity.

Human Uterine Lavage: First Live Births from In Vivo Conceived Genetically Screened Blastocysts.

We wish to report the first live births from genetically screened human euploid blastocysts obtained by uterine lavage. The embryos transferred to infertile women were previously obtained using a novel fully automated uterine lavage catheter and fluid recovery device developed for this indication. The objective of this portion of the research was to confirm embryo implantation and live births with these unique in vivo conceived blastocysts obtained by uterine lavage. In vivo conceived embryos recovered by uterine lavage 5days after intrauterine insemination were available for embryo donation. In vivo embryos were the result of prior controlled ovarian stimulation cycles in oocyte donors and intrauterine insemination with donor sperm. An observational case series of nine embryo transfer procedures was performed at an outpatient fertility center. One to two embryos were transferred to eight infertile women since one woman had two separate embryo transfer procedures. Nine embryo transfer procedures were performed with 14 blastocysts in eight women resulting in a blastocyst implantation rate of 36% (5/14) and live birth rate of 44% (4/9). Five infants have been born from the four delivered pregnancies with one set of twins. This is the first report of live births from genetically screened human euploid blastocysts obtained by uterine lavage. The nonsurgical uterine lavage office procedure represents the only current approach to obtain in vivo conceived embryos and can provide a benchmark for comparison to standard in vitro cultured blastocysts. Live births of in vivo conceived blastocysts represent the validation that the nonsurgical uterine lavage procedure allows simplified access to naturally conceived embryos without performing the surgical procedure of an oocyte aspiration. Owing to its simplicity, uterine lavage may be useful in screening embryos for preimplantation genetic testing for aneuploidy in fertile and infertile couples. ClinicalTrials.gov (Identifier NCT03426007).

The pregnancy results were not affected from the administration day of Depot GnRH agonists in artificial cycle frozen-thawed embryo transfers

Aim: In frozen-thawed embryo transfers (FET), Gonadotropin-Releasing Hormone (GnRH) agonists have recently been used to improve implantation results. It is preferred to administer it in the luteal phase of the previous cycle. The objective was to compare the effects of different administration days of depot GnRH agonists on implantation and pregnancy rates in the artificial cycle of FET.
 Material and Method: A retrospective case-control study was conducted in an in vitro fertilization (IVF) center in a university hospital, including all women starting an artificial cycle of FET. One thousand two hundred and twenty-seven (n:1227) FET cycles were scanned from the files from October 2014 to December 2021. Depot agonists (Lucrin depot 3.75 mg sc Abbott USA.-leuprolide acetate) were used in 219 patients with endometriosis. In 58 patients, it was administered on day 21 of the previous cycle (Group 1), and in 161 patients, it was administered on day 2 of the same cycle (Group 2).
 Results: This study showed no statistically significant difference between the two groups in laboratory parameters and endometrial thickness (p>0.05). There was no statistically significant association between the abort rate and transfer day (p>0.05). There was no statistically significant association between the pregnancy results and transfer day (p>0.05). The ongoing pregnancy rate (OPR) rate was relatively high in the second group compared to the twenty-first day of the previous cycle (87/161(54%) vs. 30/58 (51.7%)). The biochemical pregnancy was relatively high in the second-day group compared to the twenty-first day of the previous cycle (62/161(38.5%) vs. 21/58 (36.2%)). The abort rate was relatively high in the twenty-first-day group compared to the second day of the cycle (25/87(28.75%) vs. 9/30(30%)).
 Conclusion: In conclusion, the impacts of various administration days of depot Gonadotropin-releasing hormone (GnRH) agonists on implantation and pregnancy rates were not statistically significant.

The effect of azoospermia factor microdeletions on intracytoplasmic sperm injection results in azoospermia patients.

Y chromosome abnormalities are common in male patients with severe oligo-azoospermia. In studies with karyotype analysis and cytogenetic methods, the importance of the Y chromosome in spermatogenesis has been well understood. Deletions in the azoospermia factor (AZF) localized at the distal end of the Y chromosome adversely affect the spermatogenesis process. Our objective was to determine the frequency of AZF microdeletion in azoospermia patients who underwent microTESE. In this retrospective cohort study, 806 azoospermic men attending the In Vitro Fertilization (IVF) Center for infertility treatment between 2010 and 2022 were included. AZF deletion screening was conducted in all patients included in the study. Azoospermic patients with and without Y microdeletion were matched with the female's age, cause of infertility, number of oocytes retrieved and number of metaphase II (MII) oocytes produced and compared. The primary outcome was the live birth rate (LBR). Pregnancy rate (PR) and clinical pregnancy rates (CPR) were secondary outcomes. We detected Y microdeletion in 55 (6.82%) of 806 infertile azoospermic men and 35 of them included in the study. Although the required gonadotropin dose and the total number of retrieved oocytes were similar, clinical pregnancy rates and live birth rates were found to be significantly lower in the microdeletion patient group (21.6% vs. 43%, p<0.05; and 18.9% vs. 36%, p<0.05, respectively). Poor sperm quality in AZF microdeletion patients complicates the selection of appropriate sperm for ICSI. Therefore, it leads to a decrease in embryonic development, fertilization and pregnancy results. In order to select the best sperm for the use in ICSI procedure in this patient population, intracytoplasmic morphologically selected sperm injection (IMSI) method can be preferred to improve the cycle outcomes.

Impact of COVID-19 Pandemic on Women's Health and Obstetric Outcomes after Assisted Reproduction: A Survey from an Italian Fertility Center.

the restrictive measures that were adopted during three waves of the COVID-19 pandemic had an impact on both the emotional state and lifestyle of the general population. We evaluated the impact of COVID-19 pandemic on lifestyles and emotional states of women planning assisted reproductive technology (ART), and whether these changes affected ART outcomes. quantitative research, using a web-based survey, was performed on 289 Caucasian women. In preconception, we observed higher percentage of women with positive obstetric outcomes who reduced body weight (52.4% vs. 27.2%, p = 0.09). Over 60% of women with positive outcomes practiced physical activity vs. 47% of women with negative outcomes (p = 0.03), as well as having better quality of sleep (45% vs. 35%), and a more solid relationships with their partners (65.1% vs. 51.7%, p = 0.03). Women who increased their intake of whole grains, fruits, vegetables, and legumes (p < 0.05), according to the Mediterranean diet, showed positive outcomes. We observed that participants who experienced "very much" or "extreme" anxiety, sadness, and fear (p < 0.05) during pandemic were clearly more numerous in the group with negative pregnancy outcomes. healthy lifestyle together with a positive emotional state in preconception can positively influence the obstetric outcomes after ART.

Effect of Distance From Fertility Center on Utilization of Fertility Preservation Referral in Men.

Fertility preservation (FP) is underutilized in males with cancer or other diseases requiring gonadotoxic therapies. We sought to evaluate whether patient distance from FP center affected rates of providing a semen analysis after referral. We performed a retrospective analysis of all males who were referred for FP at a single institution between 2013 and 2021. A multiple logistic regression model was conducted with semen sample submission as the variable of interest. Predictor variables were disease type, distance, and payment method. Secondary outcomes were number of semen samples submitted and number of vials collected. Records of 461 males referred to our center were analyzed. Of these patients, 326 (71%) provided a semen sample after referral and 135 (30%) did not. Further distance from our center was associated with lower odds of submitting a semen sample (OR, 0.85; 95% CI, 0.75 to 0.97; P < .05). For patients who submitted at least one sample, distance did not affect the total number of samples submitted but was associated with a small increase in total vials cryopreserved. Men referred for FP exhibit a high rate of sperm cryopreservation. Further distance from FP center was associated with decreased odds to provide semen sample after referral. Our model estimated a 15% decrease in odds of collection with every doubling of distance from our center. Efforts must be made to improve FP utilization for patients traveling far distances, but distance alone should not preclude referral.

Nonerythroid hemoglobin promotes human cumulus cell viability and the developmental capacity of the human oocyte

To determine the relationship between the levels of cumulus cell (CC) hemoglobin messenger ribonucleic acid (mRNA) and the developmental potential of the associated oocyte and whether hemoglobin protects the CCs from oxidative stress-induced apoptosis. Laboratory-based study. University laboratory and university-affiliated invitro fertilization center. Cumulus cells from the oocytes of patients who underwent invitro fertilization with intracytoplasmic sperm injection with and without preimplantation genetic testing between 2018 and2020. Studies on individual and pooled CCs collected at the time of oocyte retrieval or cultured under 20% or 5% O2. Quantitative polymerase chain reaction analysis of individual and pooled patient CC samples were used to monitor the hemoglobin mRNA levels. Reverse transcription-polymerase chain reaction arrays were used to assess genes that regulate oxidative stress in CCs associated with aneuploid and euploid blastocysts. Studies were conducted to assess the effect of oxidative stress on the rate of apoptosis, level of reactive oxygen species, and gene expression in CCs invitro. Compared with CCs associated with arrested and aneuploid blastocysts, the mRNA levels encoding the alpha and beta chains of hemoglobin increased by 2.9- and 2.3-fold in CCs associated with euploid blastocysts, respectively. The mRNA levels encoding the alpha and beta chains of hemoglobin also increased by 3.8- and 4.5-fold in CCs cultured under 5% O2 vs. 20% O2, respectively, and multiple regulators of oxidative stress were overexpressed in cells cultured under 20% O2 compared with those under 5% O2. However, the rate of apoptosis and amount of mitochondrial reactive oxidative species increased by 1.25-fold in CCs cultured under 20% O2 compared with those under 5% O2. Variable amounts of the alpha and beta chains of hemoglobin were also detected within the zona pellucida and oocytes. Higher levels of nonerythroid hemoglobin in CCs are associated with oocytes that result in euploid blastocysts. Hemoglobin may protect CCs from oxidative stress-induced apoptosis, which may enhance cumulus-oocyte interactions. Moreover, CC-derived hemoglobin may be transferred to the oocytes and protect it from the adverse effects of oxidative stress that occurs invivo and invitro.

Does endometrial thickness affect birth weight and serum levels of pregnancy-associated plasma protein-A in frozen cycles?

ObjectiveTo investigate whether endometrial thickness (EMT) affects birth weight and maternal serum pregnancy-associated plasma protein-A (PAPP-A) level in singleton pregnancies following frozen–thawed blastocyst transfer (FET). MethodsThis retrospective study included women who underwent first-trimester combined screening for aneuploidy after FET, and subsequently delivered a singleton live birth after 24 weeks of gestation at a private in-vitro fertilization centre. The subjects were stratified into three groups based on EMT percentiles: <7.7 mm (<10th percentile), 7.7–12 mm (10–90th percentile), and > 12 mm (>90th percentile). Multi-variable linear regression analysis was undertaken to identify the association between birth weight and EMT after adjusting for variables with p < 0.1 on univariate analysis. ResultsIn total, 560 women met the inclusion criteria. Mean (±standard deviation) birth weight was 3127 ± 783 g in those with EMT < 7.7 mm, 3225 ± 644 g in those with EMT 7.7–12 mm, and 3256 ± 599 g in those with EMT > 12 mm (p = 0.577). Mean PAPP-A and PAPP-A < 0.5 rates were similar in the three groups. On multi-variate analysis, maternal serum PAPP-A was found to be a significant predictor of birth weight (p = 0.013), but EMT was not found to be predictive of birth weight on univariate or multi-variate analysis. ConclusionThis study provided a new angle to evaluate the association between EMT and neonatal birth weight by analysing this association along with maternal serum PAPP-A as a marker for placental function, suggesting that EMT is not an independent factor for neonatal birth weight.

Impact of duration of Infertility on the Physiological Viability of Sperms Preparing for Intrauterine Insemination among Yemeni Infertile Males

Background :The duration of infertility should be considered as a factor that may affect the outcome of assisted reproductive techniques (ART).Aim :The aim of this descriptive study was to examine the outcome of infertility treatment in relation to duration of infertility. Methods: Sixty nine couples from Allow in vitro fertilization center (IVF) were involved in this work. Intrauterine insemination (IUI) had been done for all couples using the same ART. Results: The mean age of men was 29.37±0.16 years and the duration of infertility was 4.38±0.25 years with range of 1-12 years. Higher pregnancy and life-birth rates were demonstrated in males suffering from infertility for less than 4 years as compared to those who had infertility for more than 10 years (P&lt;0.003, r = -0.869). Moreover, abortion rate was higher in men who had infertility for more than 10 years as compared to those who have infertility for less than 4 years (P&lt;0.0014).. The linear life-birth rate, in both IVF centers, shows decrease by increase in the duration of infertility. Conclusion: The researchers conclude that by increase in the duration of infertility the outcome of assisted reproductive techniques –IUI will be decreased markedly. In addition to the duration of infertility, the present work recommended to consider the different techniques of sperm preparation in relation to the ART outcome.

Intake of soy products and soy isoflavones in relation to ovarian reserve

To investigate the association between intake of soy food and isoflavone with ovarian reserve. Previous studies suggest on the relationship between soy intake and human fertility are inconsistent. Some clinical studies suggest that soy and phytoestrogens may not be deleterious to reproduction and may even be beneficial in couples undergoing infertility treatment. However, no studies have evaluated the relationship between soy or isoflavone intake with markers of ovarian reserve other than follicle-stimulating hormone (FSH). Cross-sectional study. An academic fertility center. Patients presenting to an academic fertility center between 2007 and 2019 were invited to participate in the Environment and Reproductive Health Study. Six hundred and sixty seven participants reported their soy food intake and had an antral follicle count (AFC) assessment. Intake of 15 soy-based foods during the previous 3 months was obtained at baseline and intake of isoflavone was estimated. Participants were divided into 5 groups based on soy food and isoflavone intake considering those who did not consume soy as the reference group. Ovarian reserve was assessed using AFC as the primary outcome measure, with antimüllerian hormone (AMH) and FSH as secondary outcome measures. The AFC was measured on the third day of the menstrual cycle. Moreover, FSH and AMH levels were measured in blood samples obtained on the third day and the follicular phase of the menstrual cycle. To evaluate the association between soy intake and ovarian reserve, we used Poisson regression models for AFC and quantile regression models for AMH and day 3 FSH levels by adjusting for confounders. Participants had a median age of 35.0 years. The median intake of soy was 0.09 servings/day and isoflavones was 1.78 mg/day. Moreover, AFC, AMH, and FSH were unrelated to soy intake in crude analyses. We found no association between soy food intake with AFC or day 3 FSH level in multivariable models. However, participants in the highest category of soy food intake had significantly low AMH levels (-1.16, 95% confidence interval: -1.92, -0.41). Soy intake had no association with AFC, AMH, or FSH in sensitivity analyses that included using different cutoff points of soy intake, excluding participants in the highest 2.5 percentile of intake, and additional statistical adjustment for dietary patterns. The results of this study are not consistent with a strong positive or inverse association of soy or isoflavone intakes within the observed range of intake, which substantially overlaps with that in the general population of the United States as well as the ovarian reserve among individuals presenting to fertility centers.

Serum persistent organic pollutants and diminished ovarian reserve: a single-exposure and mixture exposure approach from a French case-control study.

Are persistent organic pollutants (POPs) associated with a diminished ovarian reserve (DOR) in women of reproductive age? Amongst 17 POPs detected in over 20% of serum samples, only p,p'-DDE was significantly associated with an increased risk of DOR, and β-hexachlorocyclohexane (β-HCH) was significantly associated with a decreased risk of DOR whilst mixture analyses yielded non-significant associations and did not detect any interactions between POPs. Animal studies have shown that several POPs can alter folliculogenesis and increase follicle depletion. However, only a few studies have been conducted in humans, with small sample sizes and inconsistent results. Our study included 138 cases and 151 controls from the AROPE case-control study. Study participants were women between 18 and 40 years of age recruited amongst couples consulting for infertility in four fertility centres in western France between 2016 and 2020. Cases of DOR were defined as women with anti-Müllerian hormone (AMH) levels ≤1.1 ng/ml and/or antral follicle count (AFC) <7, and controls were women with AMH levels between 1.1 and 5 ng/ml and AFC ≥ 7, without genital malformations and with a menstrual cycle length between 26 and 35 days. A total of 43 POPs (including 15 organochlorine pesticides, 17 polychlorinated biphenyls, and 9 polybromodiphenylethers) were measured in the serum at inclusion into the study. We conducted logistic regression adjusted for potential confounders using a directed acyclic graph to study the effect of each POP on DOR as single exposures, and used Bayesian kernel machine regression (BKMR) to measure the mixture effect of POPs on DOR. Of the 43 POPs, 17 were detected in over 20% of the serum samples. In the single-exposure multivariate logistic regressions, p,p'-DDE (median 165.0 IQR 161.0 ng/l in controls) as a continuous exposure was significantly associated with an increased risk of DOR (odds ratio (OR) 1.39, 95% CI 1.10-1.77) and non-significantly associated with an increased risk of DOR for the second and third terciles (OR 1.46, 95% CI 0.74-2.87, and OR 1.72, 95% CI 0.88-3.37, respectively). β-HCH (median 24.2 IQR 21.5 ng/l in controls) was significantly associated with a decreased risk of DOR when β-HCH was treated as a continuous exposure (OR 0.63, 95% CI 0.44-0.89) and for the third tercile of exposure (OR 0.43, 95% CI 0.21-0.84) and non-significantly associated with a decreased risk of DOR for the second tercile (OR 0.77, 95% CI 0.42-1.42). All sensitivity analyses confirmed our results. BKMR showed similar associations for single exposures but found no significant associations for the total mixture effect. In addition, the BKMR results did not suggest any interactions between POPs. Controls were recruited amongst infertile couples and thus may not be representative of all women of reproductive age. However, their POP concentrations were in the same range as in the general French population. This study is the first to examine the associations between serum POPs and DOR. The well-recognized anti-androgenic properties of p,p'-DDE and estrogenic properties of β-HCH could explain these associations of opposite direction. If these results are replicated elsewhere, this could have an impact on fertility prevention messages and help in understanding the impact of POPs on the female reproductive system. This study was funded by the Fondation de France (grant numbers 2014-50537 and 00110196) and the French Biomedicine Agency (2016). None of the authors have any conflicts of interest to declare. N/A.

Perspectives and Psychological Impact of Infertile Couples on Postponement of Fertility Treatment Due to COVID-19 Pandemic: A Cross-Sectional Study

Introduction: Coronavirus disease 2019 (COVID-19) brought forth an unprecedented suspension of fertility treatment worldwide as part of a reallocation of hospital staff and resources to avoid a collapse in the healthcare system. As a nonessential service, postponement of fertility treatment due to the pandemic has impacted the mental health of infertile patients, which comprise [Formula: see text] of the Malaysian population. Objective: To establish the patient’s perspective on how the COVID-19 pandemic has affected their fertility treatment and to ascertain their psychological status. Methods: This was a cross-sectional study performed in a single academic center in Malaysia. This study was approved by the Universiti Malaya Medical Centre (UMMC) medical research ethics committee (MEC ID NO: 2021714-10376). Patients and partners who were planned for fertility treatment were approached and asked to answer an anonymous electronic survey between July 16, 2021 and December 17, 2021. All patients requiring fertility treatment were included. Results: One hundred and sixty-five patients were included, and [Formula: see text] of patients did not agree with the Ministry of Health Malaysia’s recommendation to postpone fertility treatment; [Formula: see text] would want to continue with treatment; [Formula: see text] of patients are concerned about advancing age and [Formula: see text] are concerned about reducing ovarian reserve if their treatment was postponed or suspended. From univariate analysis, mild, moderate, severe, and extremely severe levels of psychological disorders were found in our patients. According to multivariate logistic regression, mild stress was significant among 20–30 years old with [Formula: see text] (OR [Formula: see text], [Formula: see text] CI [Formula: see text]). Patients from this age group also suffer from a significant moderate level of stress with [Formula: see text] (OR [Formula: see text], [Formula: see text] CI [Formula: see text]). Other variables, when analyzed using multivariate analysis, had no significant findings. Conclusion: Stress related to COVID-19 and concerns about its effect on the fertility rate were found to be significant psychological distress among patients undergoing fertility treatment. Therefore, fertility centers should routinely monitor the mental health of patients and offer them psychological counseling.

Analysis of follicular fluid and serum markers of oxidative stress in women with unexplained infertility by Raman and machine learning methods

AbstractOocytes are surrounded by a fluid called follicular fluid, which provides an essential microenvironment for developing oocytes in human fertility. Various molecules exist in antral follicles, including proteins, steroid hormones, polysaccharides, metabolites, reactive oxygen species, and antioxidants. Oxidative stress is involved in the etiology of defective oocyte development or poor oocyte and embryo quality. Raman spectroscopy, a noninvasive method, can be used for biological diagnostics and direct chemical identification of follicular fluid. Therefore, we measured the oxidative index of follicular fluids and then attempted Raman spectroscopy on the follicular fluids combined with machine learning techniques to identify, detect, and quantify follicular fluid of unexplained infertility‐diagnosed women as a safe and effective tool to use as adjacent for clinical studies. This was a retrospective study set in an academic hospital where the patients were selected from an unexplained infertility‐diagnosed population in the in vitro fertilization (IVF) center. Raman spectra of 128 follicular fluid samples (n = 63 control; and 65 unexplained infertility) were obtained. To profile Raman‐based results of follicular fluid, oxidative load measurements, multivariate analysis, correlation tests, and six machine learning methods were used. Raman bands associated with oxidative load and amide III and lipids differed significantly. Classification using stacks of Raman signals was applied by random forest, C5.0 decision tree algorithm, k‐nearest neighbors, deep neural networks, support vector machine, and XGBoost trees algorithms achieved an overall accuracy of 92.04% to 99.17% in assigned correctly. Group has an oxidative load in their follicle fluids consistent with clinical results and biochemical measurements and performing testing based on Raman spectra validated by kNN clustering and SVM object vector separation machine learning methods. The study suggests that Raman spectroscopy can detect changes in follicle fluid in unexplained infertility.

Pregnancy and neonatal outcomes of letrozole versus natural cycle frozen embryo transfer of autologous euploid blastocyst.

To investigate the pregnancy and neonatal outcomes of letrozole-stimulated frozen embryo transfer (LTZ-FET) cycles compared with natural FET cycles (NC-FET). Our retrospective cohort included all LTZ-FET (n = 161) and NC-FET (n = 575) cycles that transferred a single euploid autologous blastocyst from 2016 to 2020 at Stanford Fertility Center. The LTZ-FET protocol entailed 5mg of daily letrozole for 5days starting on cycle day 2 or 3. Outcomes were compared using absolute standardized differences (ASD), in which a larger ASD signifies a larger difference. Multivariable regression models adjusted for confounders: maternal age, BMI, nulliparity, embryo grade, race, infertility diagnosis, and endometrial thickness. The demographic and clinical characteristics were overall similar. A greater proportion of the letrozole cohort was multiparous, transferred high-graded embryos, and had ovulatory dysfunction. The cohorts had similar pregnancy rates (67.1% LTZ vs 62.1% NC; aOR 1.31, P = 0.21) and live birth rates (60.9% LTZ vs 58.6% NC; aOR 1.17, P = 0.46). LTZ-FET neonates on average were born 5.7days earlier (P < 0.001) and had higher prevalence of prematurity (18.6% vs. 8.0%NC, ASD = 0.32) and low birth weight (10.4% vs. 5.0%, ASD = 0.20). Both cohorts' median gestational ages (38weeks and 1day for LTZ; 39weeks and 0day for NC) were full term. There were similar rates of pregnancy and live birth between LTZ-FET and NC-FET cycles. However, there was a higher prevalence of prematurity and low birth weight among LTZ-FET neonates. Reassuringly, the median gestational age in both cohorts was full term, and while the difference in gestational length of almost 6days does not appear to be clinically significant, this warrants larger studies.

The Influence of Maternal KIR Haplotype on the Reproductive Outcomes after Single Embryo Transfer in IVF Cycles in Patients with Recurrent Pregnancy Loss and Implantation Failure—A Single Center Experience

(1) Background: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) have in common a deficient maternal adaptation to the semi-allogeneic fetus, in which killer immunoglobulin-like receptor (KIR) family expressed by natural killer (NK) cells play an important role. The aim of this study was to evaluate the influence of maternal KIR haplotype on the reproductive outcomes after single embryo transfer in IVF cycles in patients with RPL and RIF. (2) Methods: Patients with RIF and RPL who presented at Origyn Fertility Center from Iasi, Romania, were prospectively enrolled between January 2020 and December 2022. Clinical and paraclinical data was examined. Descriptive statistics and a conditional logistic regression model were used to analyze our data. (3) Results: Patients with a KIR AA haplotype had significantly more chances of miscarriage if they underwent an IVF procedure (aOR: 4.15, 95% CI: 1.39-6.50, p = 0.032) compared with those who spontaneously achieved a pregnancy. Moreover, it appeared that the same haplotype increased the chances of obtaining a pregnancy for patients who underwent an IVF procedure (aOR: 2.57, 95% CI: 0.85-6.75, p = 0.023). (4) Conclusions: Determination of KIR haplotype could be beneficial for patients with RPL or RIF in order to offer an individualized management.

Age-related methylation changes in the human sperm epigenome.

Advanced paternal age is associated with increased risks for reproductive and offspring medical problems. Accumulating evidence suggests age-related changes in the sperm epigenome as one underlying mechanism. Using reduced representation bisulfite sequencing on 73 sperm samples of males attending a fertility center, we identified 1,162 (74%) regions which were significantly (FDR-adjusted) hypomethylated and 403 regions (26%) being hypermethylated with age. There were no significant correlations with paternal BMI, semen quality, or ART outcome. The majority (1,152 of 1,565; 74%) of age-related differentially methylated regions (ageDMRs) were located within genic regions, including 1,002 genes with symbols. Hypomethylated ageDMRs were closer to transcription start sites than hypermethylated DMRs, half of which reside in gene-distal regions. In this and conceptually related genome-wide studies, so far 2,355 genes have been reported with significant sperm ageDMRs, however most (90%) of them in only one study. The 241 genes which have been replicated at least once showed significant functional enrichments in 41 biological processes associated with development and the nervous system and in 10 cellular components associated with synapses and neurons. This supports the hypothesis that paternal age effects on the sperm methylome affect offspring behaviour and neurodevelopment. It is interesting to note that sperm ageDMRs were not randomly distributed throughout the human genome; chromosome 19 showed a highly significant twofold enrichment with sperm ageDMRs. Although the high gene density and CpG content have been conserved, the orthologous marmoset chromosome 22 did not appear to exhibit an increased regulatory potential by age-related DNA methylation changes.

Using an Interpretable Machine Learning Model to Predict Corifollitropin Alfa Protocol

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