Risk Of Infertility Research Articles

The Role of the Primary Care Physician in the Assessment and Management of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous female endocrine disorder with manifestations that span the hormonal, reproductive, metabolic, and psychological. Primary care physicians (PCPs), also known as family physicians or general practitioners, play a key role in the diagnosis, assessment, and management of PCOS. This article outlines the role of the PCP in the timely and accurate diagnosis, provision of information and education, lifestyle and weight management, and management of key features such as hyperandrogenism, irregular cycles, infertility, emotional well-being, and cardiometabolic risk. PCPs play an essential role as the point of first contact for women and adolescents with or at high risk of PCOS, providers of whole-person care and continuity of care, and coordinators of care within a multidisciplinary team. Optimal management of PCOS requires equitable access to primary care. There is a need for systemic approaches to addressing barriers to provision of quality primary care, such as poor remuneration of longer consultations and low awareness of evidence-based guidelines, to women and adolescents with PCOS.

Sleep disorders and risk of infertility: A meta-analysis of observational studies.

The purpose of this study was to determine the relationship between sleep disorders and risk of infertility. Three databases (PubMed, Embase, and Cochrane Library) were searched form their inception to April 30, 2023. Information of study design, control group and experimental group, number of participants, and study outcomes was extracted. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS scale) and the Agency for Healthcare Research and Quality (AHRQ scale). Narrative synthesis and meta-analysis were used to analyze these studies. Eight cohort, cross-sectional, and case-control studies were considered. The reviewed studies were high-quality. Pooled analysis showed that the risk of infertility was 1.43-fold higher in patients with sleep disturbance (HR = 1.43, 95% CI, 0.97-2.11, z = 1.79), but this was not statistically different; the risk was 1.58-fold higher in patients with OSA compared to those without OSA (HR = 1.58, 95%, CI, 0.99-2.52, z = 1.91), but this was not statistically significant. Wake-up time is also associated with infertility (OR = 1.14; 95%CI = 1.01-1.28; P = 0.037). For every hour they stay awake beyond 8:00 AM, participants had a 41% higher risk of infertility (P = 0.004). The early-to-bed/late-to-rise (EL), LE, and LL groups had a higher risk of infertility than the EE group. The present study did not find an association between sleep disorders and the risk of infertility. Therefore, more observational studies are warranted to explore the association between sleep disorders and the risk of infertility.

Adverse drug reactions on male fertility

For several years, fertility disorders have been on the increase worldwide. These disorders affect both sexes, but are more pronounced in men; and in half of cases the etiology is unknown. The role of drugs in male infertility has been little studied to date. Most of the available data comes from experimental animal studies, with all their limitations. With the exception of a few drugs, such as certain anticancer agents, human data are rare. This article describes the mainly drugs known to have deleterious effects on male fertility, the mechanisms leading to these effects and methods used to assess the risk of drug-induced male infertility. It underlines the need for further work in experimental research, clinical trials and post-marketing surveillance to improve our knowledge of drugs that induce male infertility. Although these adverse effects are not life-threatening, they can have a significant impact on patients' lives.

Review on Polycystic Ovarian Syndrome (PCOS) In Case of Pregnancy

Women with polycystic ovary syndrome (PCOS) have a higher risk of infertility, miscarriage, obesity, cardiovascular disease, diabetes mellitus, obstructive sleep apnea, depression, nonalcoholic fatty liver disease, endometrial hyperplasia, and cancer. Women with PCOS are more likely to undergo cesarean or c-section deliveries, which are associated with a high risk of early pregnancy loss. The most effective therapies for PCOS include regular exercise, a good diet, and weight management. In fact, the harmful consequences of obesity on reproductive potential can be reversed with effective therapy, whether or not there is insulin resistance. Based on the outcomes of trials conducted in recent years, this promise appears to be coming true.

Torsion of Undescended Testis Mimicking Acute Appendicitis: Case Report

Cryptorchidism or undescended testis (UDT) is one of the most common urological disorders in boys. UDT is usually linked to an increased risk of infertility and testicular malignancy, but also to a higher and significant risk of torsion. Yet, torsion of UDT represents an unusual mode of revelation of cryptorchidism, especially in adults. Symptoms mainly include acute abdominal pain, simulating an acute appendicitis when the right testicle is affected. This uncommon clinical presentation may be responsible for delayed diagnosis and management. Thus, genital examination is important to be performed by physician in the emergency room when a male patient presents acute abdominal pain. When the torsion of an UDT is clinically suspected, no medical imaging should delay surgical exploration. Any delay in the management may affect salvage of the gland and lead to orchiectomy. In this case report, we are reporting the case of a young male who was seen in the emergency room for acute abdominal pain mimicking an acute appendicitis. Physical examination and radiological investigation confirmed the diagnosis of torsion of a right UDT.

Association of GSTM1 Polymorphism and Redox Potential with Idiopathic Male Infertility.

The aim of this case-control study is to investigate possible associations between GSTM1 polymorphism and redox potential with sperm parameters. The study group consisted of sperm samples from 51 infertile men according to the WHO guidelines. The control group included 39 samples from men with normal seminal parameters. DNA was extracted and genotyped for the detection of the GSTM1 polymorphism. An evaluation of the static redox potential (sORP) using the MiOXSYSTM system was conducted. The frequency of the GSTM1-null genotype was higher in infertile male individuals (60.78%) than in the controls (41.03%) and was associated with a 2.228-fold increased risk for male infertility. Fertile controls carrying the GSTM1-null genotype presented a lower percentage of typical sperm morphology and lower slow progressive motility. An excess of redox potential was observed in infertile males compared to fertile ones. In the control group higher sORP values had a positive correlation with immotility percentage and a negative correlation regarding total motility. In the study group sORP values had a negative correlation with total count, concentration, and slow progressive motility. The present study highlights that GSTM1 polymorphism and redox potential affect both fertile and in fertile males. Moreover, redox potential levels could be used as an additional indicator along with the routine semen analysis for a comprehensive screening between infertile and fertile men.

Unraveling the Genetic Associations of DENND1A (rs9696009) and ERBB4 (rs2178575) with Infertile Polycystic Ovary Syndrome Females in Pakistan.

PolycysticOvary Syndrome (PCOS) is a complex genetic disorder in reproductive-aged women which is associated with comorbidities of reproductive, metabolic, cardiovascular, endocrine, and psychological nature. PCOS is the most common cause of anovulatory infertility. Pathogenesis of PCOS involves strong interaction between environmental and genetic factors. Many Single-Nucleotide Polymorphisms (SNPs) have been associated with PCOS in different populations. Currently, very limited association studies of PCOS and infertility have been done on Pakistani population. The variants DENND1A rs9696009 and ERBB4 rs2178575 are significantly associated with PCOS in Chinese and European populations. These candidate genes regulate the production of androgen hormone, Anti-Mullerian Hormone (AMH), and luteinizing hormone. All these hormones are involved pathogenesis of PCOS and infertility. The aim of the study is to find an association of DENND1A rs9696009 and ERBB4 rs2178575 variants with PCOS in infertile Pakistani females. In this case-control study, 300 infertile females were recruited. The cases (n = 160) were infertile female diagnosed with PCOS (Rotterdam Criteria), and controls (n = 140) were infertile women with no evidence of PCOS. The genomic DNA was isolated, and genotyping was done by PCR-Restriction fragment length polymorphism and further validated by DNA Sanger Sequencing. The Chi-Square analysis showed rs2178575 (ERBB4) was significantly associated with infertility (χ2 = 10.282, p = 0.005852) while rs9696009 (DENND1A) did not show any significant association (χ2 = 3.10, p = 0.212036). Furthermore, multinomial logistic regression analysis was performed and revealed that rs2178575 (ERBB4) heterozygous genotypes (GA) and mutant genotypes (AA) decrease the risk of infertility by 0.541 times (OR = 0.541, 95% CI = 0.314-0.930, p = 0.026) and 0.416 times (OR = 0.416, 95% CI = 0.228-0.757, p = 0.004), respectively, compared to wild-type genotype (GG). The ERBB4 variant is significantly associated with PCOS infertile women and genetically indicated that ERBB4 (rs2178575) decreases the risk of infertility in females having PCOS.

Associations of semen quality with pyrethroids in semen and urine samples of men with oligozoospermia: A cross-sectional study in Samsun, Turkey.

Pyrethroids (PYRs) may act as endocrine disrupters and lead to infertility. The aim of the study was to analyze the levels of anti-androgenic PYRs (cypermethrin, deltamethrin, and permethrin) and 3-phenoxy benzoic acid (3-PBA), a general metabolite of PYRs, in both semen and urine samples of men with oligozoospermia. The PYRs and 3-PBA metabolite levels in the semen and urine samples of the men were analyzed through GC-MS. The results indicated that the levels of PYRs in the semen samples of the infertile group were significantly higher than those of the fertile group. It was determined that cypermethrin exposure was associated with changes in sperm count and total sperm motility, while permethrin, deltamethrin, and 3-PBA levels were associated with changes in sperm morphology. It was determined that there was a significant negative correlation between semen deltamethrin levels and sperm morphology and sperm count. In addition, exposure of these patients to deltamethrin (range; 1.53-8.02µg/l) and having farmer parents were determined to increase the risk of infertility. In conclusion, the findings of this study showed that exposure to environmental PYRs may adversely affect semen quality, especially in terms of sperm morphology, in men with oligozoospermia.

The relationship between cesarean delivery and fecundability: a population-based cohort study

BackgroundPrevious studies have found that women with caesarean delivery have fewer pregnancies. Caesarean delivery is also more common among women with lower fecundability. The potential role of caesarean delivery on reduced fecundability is not known. ObjectiveTo assess the bidirectional relationship between caesarean delivery and fecundability. Study DesignThis is a prospective cohort study based on data from the Norwegian Mother, Father, and Child Cohort study linked with the Medical Birth Registry of Norway. We estimated the fecundability ratio (per cycle probability of pregnancy) and relative risk of infertility (time to pregnancy ≥ 12 months) according to mode of delivery in the previous delivery among 42,379 women. For the reverse association, we estimated the relative risk of having a caesarean delivery by fecundability (the number of cycles women needed to conceive) among 74,025 women. ResultsThe proportion of women with infertility was 6.2% (2711/43936) among women with prior vaginal delivery, and 8.6% (518/6036) among women with a prior caesarean delivery, yielding an adjusted relative risk of 1.21 (95% confidence interval: 1.10 to 1.33). Women with previous caesarean delivery also had lower fecundability ratio (0.90, 95% confidence interval 0.88 to 0.93), compared to women with prior vaginal delivery. When assessing the reverse association between fecundability and caesarean delivery, we found that women who did not conceive within 12 or more cycles had higher risk of caesarean delivery (adjusted relative risk 1.55, 95% confidence interval 1.46 to 1.64) compared to women who conceived within the first two cycles. Associations remained after controlling for sociodemographic and clinical risk factors and were observed across parity groups. ConclusionAmong women with more than one child, those who had caesarean delivery had subsequent lower fecundability ratio and increased infertility risk compared to those who had vaginal delivery. However, women who needed longer time to conceive were also more prone to be delivered by caesarean delivery. We therefore found evidence of a bidirectional relationship between caesarean delivery and fecundability. This could be due to a common underlying explanatory mechanism, and the surgical procedure itself may not directly influence fecundability.

Innovative Strategies for Fertility Preservation in Female Cancer Survivors: New Hope from Artificial Ovary Construction and Stem Cell-Derived Neo-Folliculogenesis.

Recent advances in anticancer treatment have significantly improved the survival rate of young females; unfortunately, in about one third of cancer survivors the risk of ovarian insufficiency and infertility is still quite relevant. As the possibility of becoming a mother after recovery from a juvenile cancer is an important part of the quality of life, several procedures to preserve fertility have been developed: ovarian surgical transposition, induction of ovarian quiescence by gonadotropin-releasing hormone agonists (GnRH-a) treatment, and oocyte and/or ovarian cortical tissue cryopreservation. Ovarian tissue cryostorage and allografting is a valuable technique that applies even to prepubertal girls; however, some patients cannot benefit from it due to the high risk of reintroducing cancer cells during allograft in cases of ovary-metastasizing neoplasias, such as leukemias or NH lymphomas. Innovative techniques are now under investigation, as in the construction of an artificial ovary made of isolated follicles inserted into an artificial matrix scaffold, and the use of stem cells, including ovarian stem cells (OSCs), to obtain neo-folliculogenesis and the development of fertilizable oocytes from the exhausted ovarian tissue. This review synthesizes and discusses these innovative techniques, which potentially represent interesting strategies in oncofertility programs and a new hope for young female cancer survivors.

Perceived and Objective Fertility Risk Among Female Survivors of Adolescent and Young Adult Cancer

Fertility is important to many survivors of adolescent and young adult (AYA) cancer, yet data on this population's fertility perceptions and their alignment with objective infertility risk are scant. To assess whether estimated treatment gonadotoxicity and posttreatment menstrual pattern are associated with higher infertility risk perception. This retrospective cohort study included female young adult survivors of cancer diagnosed between ages 15 and 39 years were recruited between March 25, 2015, and September 24, 2018, from 2 state cancer registries, social media, and clinician referrals to participate in a study of posttreatment ovarian function. Data analysis occurred between March 1 and September 1, 2022. Participants reported their menstrual pattern. Estimated treatment gonadotoxicity was ascertained through medical record review. Participants reported infertility risk perception and were categorized as increased risk (feeling less fertile or unable to become pregnant) or no increased risk (feeling more or as fertile) compared with female individuals their age. Objective infertility risk was determined by estimated gonadotoxicity, menstrual pattern, and ovarian reserve testing of self-collected dried blood spots. Multivariable logistic regression identified factors associated with perceived infertility and underestimation or overestimation of infertility risk. This study included 785 female participants with a mean (SD) age of 33.2 (4.8) years at enrollment and 25.9 (5.7) years at diagnosis. Most participants self-identified their race and ethnicity as White (585 [74.5%]) and non-Hispanic (628 [78.7%]). Most participants (483 [61.5%]) perceived a higher risk of infertility compared with female participants their age. Prior exposure to moderate- or high-gonadotoxicity treatments was associated with higher odds of perceiving increased infertility risk compared with exposure to low-gonadotoxicity treatments (adjusted odds ratio [AOR], 2.73 [95% CI, 1.87-3.97] and 15.39 [95% CI, 5.52-42.96], respectively). Amenorrhea and irregular cycles were associated with higher odds of perceiving increased infertility risk (AOR, 3.98 [95% CI, 2.13-7.41] and 1.69 [95% CI, 1.19-2.40], respectively). Perceived infertility risk had minimal agreement with objective risk (κ = 0.19). Multiparity (AOR, 4.17 [95% CI, 2.61-6.64]) was associated with increased odds of underestimation, while older age (AOR, 0.94 [95% CI, 0.89-0.98]), endocrine comorbidity (AOR, 0.35 [95% CI, 0.18-0.69]), and prior infertility (AOR, 0.16 [95% CI, 0.07-0.38]) were associated with lower odds of underestimation. Multiparity (AOR, 0.48 [95% CI, 0.27-0.86]), breast cancer (AOR, 0.38 [95% CI, 0.20-0.73]), and skin cancer (AOR, 0.24 [95% CI, 0.11-0.51]) were associated with lower odds of overestimation. In this cohort study, survivors of AYA cancer had high rates of perceiving increased infertility risk but frequently overestimated or underestimated their risk. These findings suggest that counseling on infertility risk throughout survivorship may reduce misalignment between perceptions and actual risk, decrease fertility-related psychological distress, and inform family planning decisions.

Correlation between LHCGR and NR5A1 genes polymorphism and male infertility risk

IntroductionInfertility is one of the important phenomena in human reproduction. Genetic factors are the most important cause of male infertility. Here, we aimed to investigate the correlation between idiopathic male infertility and SNPs of the LHCGR (rs2293275) and NR5A1 (rs1057517779) genes in the Iranian-Azeri population. MethodsThis case-control study consisted of 100 males with infertility and 100 healthy males from the Iranian Azeri population. Genomic DNA isolation from whole blood samples and Tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS-PCR) method was used for genotyping. The data analysis was performed by chi-square (χ2) and Fisher’s exact tests. ResultsGenotyping analysis for LHCGR (rs2293275) polymorphism indicated that the frequency of C in the case group was significantly higher than in the control group (P < .05). Moreover, genotyping analysis for NR5A1 (rs1057517779) polymorphism indicated that the frequencies of the A allele and heterozygote GA genotype in the case group were significantly higher than those in the control group (P < .05). ConclusionOur study demonstrated that the SNPs of LHCGR (rs2293275) and NR5A1 (rs1057517779) genes may play a critical role in male infertility in the Iranian Azeri population. However, further studies on other ethnic origins with larger sample sizes are essential for accessing more accurate results. Moreover, functional experiments might be needed to understand the role of these polymorphisms in the molecular pathways involved in male fertility.

FIGO statement: Fertility preservation.

Fertility preservation is a growing field in reproductive medicine that may raise ethical questions. Preservation of fertility must be discussed with the patient if gonadotoxic treatment is required, whether in the case of benign or malignant pathology, or in the management of transgender identity. As a result, surgery or chemotherapy that has fewer adverse impacts on fertility should be proposed if this does not alter the prognosis of the disease. If the risk of infertility persists, then fertility cryopreservation should be proposed for children and adults of reproductive age. Sperm, oocytes, and gonadal tissue can be cryopreserved for many years. FIGO wishes to emphasize the importance of fertility preservation in the medical and surgical management of patients, and the importance of a specialized, multidisciplinary approach.

SAT408 Assessment Of Family Planning Readiness In Transgender Youth

Abstract Disclosure: R.S. Conard: None. L.J. Folsom: None. Background: Transgender individuals identify with a gender incongruent with the sex assigned at birth. Some seek medical care in the form of gender affirming hormone therapy (GAHT) or gender affirming surgery (GAS). GAHT initiated in adolescence may include GnRH analogues and cross-sex hormones. Barriers to family planning in this population include low utilization of cryopreservation and decisional regret. There is a paucity of data on the risk of infertility with GAHT, and on to what degree transgender adolescents feel informed about fertility and family planning options. Objective: To assess knowledge regarding options for family planning and fertility preservation in transgender adolescents treated with GAHT in a pediatric endocrinology gender clinic. The goal is to enhance patient education about potential effects of GAHT on fertility and options for family planning. Methods: 41 adolescent patients aged 10 years and older treated with GAHT in an urban outpatient pediatric endocrinology clinic were surveyed from January to June 2022. Survey questions were multiple choice, Likert scale, and open-ended. To be included participants were at least 10 years of age, actively followed in the clinic, and receiving GAHT at time of enrollment. Results: 41 participants completed the survey. Four (10%) expressed interest in discussing family planning with their provider at the time of survey completion. 18 (45%) were open to discussion in the future; 16 (39%) were not interested at all. 13 (32.5%) participants were planning for future parenthood, and 16 (40%) participants were undecided. Of those interested in parenthood 7 (53.8%) planned to adopt or foster. Barriers to family planning expressed included financial concerns, potential need to pause GAHT, and social stigma of transgender parenthood. 20 (50%) participants reported prior family planning discussion with their endocrinologist. Conclusion: Despite routine family planning discussions documented during visits, these may not be optimally impactful given that 50% of participants did not recall the conversations. Family planning appears to be of lower priority in this population as most desired to postpone discussions with their provider despite undergoing treatment that could influence fertility. Our findings indicate it is essential to actively identify methods to engage transgender youth in discussions related to family planning during GAHT. Presentation: Saturday, June 17, 2023

FRI556 Thyroid Autoimmunity Leading To Premature Ovarian Insufficiency (POI) In A Euthyroid Young Woman

Abstract Disclosure: P. rimal: None. M. Moeed: None. C. Musurakis: None. A. Ojha: None. W. Akhtar: None. C.P. Barsano: None. M.F. Siddiqui: None. Introduction: Premature Ovarian Insufficiency is rare in young women and affects only 0.1% before the age of 30. The causes of POI in most cases remain unidentified, with autoimmunity being responsible for 4-30% of the cases. We present the case of a young euthyroid woman who presented for the evaluation of primary amenorrhea and diagnosed with POI associated with thyroid autoimmunity. Clinical Case: A 28-year-old Afghani woman with no known co-morbidities was referred to endocrinology clinic for the work up of primary amenorrhea. She was a goitrous and had normal secondary sexual characteristics and a history of withdrawal bleeding with OCP. There was no known personal or family history of autoimmune disease. Work up revealed hypergonadotropic hypogonadism with high FSH, 55 mIU/ml[Ref range for postmenopausal woman 16.7-113], high LH, 20.28 mIU/ml [Ref range for postmenopausal woman 10.8-58.69] and low estradiol, &amp;lt;2 pg/ml. Anti-Mullerian hormone was low, &amp;lt;0.08ng/ml [RefRange 0.69-13.39] signifying inadequate ovarian reserves and pelvic ultrasound confirmed atrophic ovaries. Etiological work up revealed normal female karyotype, 46XX, and negative FMR gene mutation testing for Fragile X syndrome. Thyroid functions were normal TSH, 3.3 mIU/L (0.27-4.2) and Free T4, 1.29 ng/dl[Ref Range 0.70-2.7]. Autoimmune work up was negative for adrenal 21-OH antibody and anti-ovarian antibodies. However, patient had strongly positive thyroid peroxidase (TPO) antibodies, 613.77 mIU/L[Ref range 0.0-9.0] consistent with thyroid autoimmunity. DXA scan revealed osteopenia. Thus, the diagnosis of POI associated with thyroid autoimmunity was established. HRT with estradiol patch and progesterone was initiated. Calcium, Vitamin D supplements and fertility counseling were provided. Conclusion: Thyroid disease is the most common autoimmune disease associated with POI. Studies have shown higher risk of POI and infertility in patients with Hashimoto’s and Graves’ diseases with co-existing high titers of TPO or anti-thyroglobulin antibodies. Ovaries are subject to autoimmune attack that leads to diminished ovarian reserves. However, until now the association of isolated elevation of TPO antibodies with POI has not been established. A Study by Osuka et al. did not find any significant difference in AMH levels between TPO and non-TPO positive euthyroid women and concluded that unlike hypothyroid women, thyroid autoantibodies were not likely to influence ovarian reserves in euthyroid women. Our case is unique where POI is associated with isolated elevation of TPO antibodies in the absence of clinical thyroid disease. This signifies the possibility that ovarian failure may precede the onset of thyroid disease in patients with thyroid autoimmunity and should be suspected and treated at an early stage, before ovarian reserves are diminished. Presentation: Friday, June 16, 2023

FRI417 An Interdisciplinary Program Promoting The Adoption Of A Healthy Lifestyle Increases Insulin Sensitivity In Women With Obesity And Infertility

Abstract Disclosure: A. Forget-Renaud: None. M. Belan: None. F. Jean-Denis: None. M. Pesant: None. J. Baillargeon: Grant Recipient; Self; Ferring Pharmaceuticals, JPB received an unrestricted investigator-initiated grant from Ferring Canada, which was not for the reported study. Introduction Obesity increases the risk of ovulatory and anovulatory infertility in women, mainly through the development of polycystic ovary syndrome (PCOS). Insulin resistance contributes to the pathogenesis of PCOS and may play a role in the infertility of PCOS and non-PCOS women with overweight or obesity. Lifestyle modifications are recommended as a first-line therapy in women with PCOS or those with obesity and infertility, as it was associated with improvement in menstrual pattern and fertility outcomes. We therefore hypothesized that a lifestyle intervention may increase insulin sensitivity in women with obesity and infertility. Methods Women with obesity and infertility were randomly allocated to usual fertility care (control group, CG) or to an interdisciplinary intervention promoting the adoption of a healthy lifestyle (LSG) alone for 6 months and then combined with usual care. Insulin resistance was estimated during fasting (HOMA-IR) and a 75-g oral glucose test (Matsuda Insulin Sensitivity Index, ISI(M)), and β-cell function was estimated using the Insulin Secretion-Sensitivity Index (ISSI-2) in women not taking medication affecting insulin sensitivity (except metformin). Data were collected at baseline, 6, 12 and 18 months, and as soon as possible when the participant knew she was pregnant. We estimated the integrated change in insulin sensitivity during follow-up using the incremental area-under-the-curve of ISI(M) divided by time (iAUC-ISI(M)/time). Results Among 130 randomized participants, 105 had available data (LSG=51, CG=54). PCOS was diagnosed using the Rotterdam criteria in 63.2% of participants, equally distributed between the groups. As compared to CG, women in the LSG improved significantly more their ISI(M) after 6 months (+0.24 [IQR: -0.48 - +0.94] vs 0.16 [-1.32 - +0.53], p=0.039, n=90), as well as their iAUC-ISI(M)/time during follow-up (+0.18±0.84 vs -0.21±0,93, p=0.035, n=104). All these results remained statistically significant after correction for baseline BMI, age and use of folic acid. Increases in iAUC-ISI(M)/time in the intervention vs control groups were significantly more important (p for interaction=0.045) in participants with baseline ISI(M) above the median (LSG: +0.10±1.13, n=24, vs CG: -0.62±1.13, n=27, p=0.028) than in those below the median (LSG: +0.26±0.48, n=27, vs CG: +0.21±0.35, n=26, p=0.71). Interactions with PCOS status and other subgroups were not statistically significant. There was no impact on HOMA-IR or ISSI-2. Conclusion An interdisciplinary program promoting the adoption of a healthy lifestyle significantly increases whole-body insulin sensitivity in women with infertility and obesity, mainly in those with higher baseline insulin sensitivity. It may be explained in part by the weight loss associated with the intervention and may have a role in improving fertility in this population. Presentation: Friday, June 16, 2023

B-189 Evaluate the suitability of urinary reference intervals for organophosphate flame retardants in healthy adult population from Southern Taiwan

Abstract Background Organophosphorus flame retardants (OPFRs) are chemical additives used to prevent fires and are widely used in furniture, electronics, plastics, and building materials. Its chemical structure is similar to human hormones, which are often misidentified and used in the human body, thereby interfering with the operation of normal physiological functions and causing endocrine system disorders, so it is also known as environmental hormones. Recently, it has been confirmed that exposure to OPFRs can cause health hazards such as neurotoxicity, endocrine disruption, hepatotoxicity, and reproductive dysfunction. In view of the increasing concern about the exposure of human OPFRs, but there is no laboratory in Taiwan to detect the content of human OPFRs. This study aims to develop a biomonitoring method for OPFRs, which is used to provide reliable information on the exposure status of individual OPFRs, and to establish a reference interval for OPFRs in the urine of different diseases and reference groups and confirm the potential of OPFRs as biomarkers in environmental medicine. Methods The Waters ACQUITY UPLC I-Class and Xevo TQ-XS IVD systems were developed to detect 10 OPFRs in urine: Tri-(n-butyl) phosphate (TNBP), Tris-(2-butoxyethyl) phosphate (TBEP), Tris-(1,3- dichloro-2-propyl) phosphate (TDCPP), Triphenyl phosphate (TPHP), Tris-(2-chloroethyl) phosphate (TCEP), Di-n-butylphosphate (DNBP), Bis-(butoxyethyl)-Phosphate (DBEP), Bis-(1,3-dichloro-2-propyl) phosphate (BDCPP), Diphenyl phosphate (DPHP), Bis (2-chloroethyl) phosphate (BCEP), and analytical methods. According to the CLSI C62A specifications, the methodology verification and confirmation passed the evaluation. A total of 538 patients (78 infertility, 167 hemodialysis, 96 esophageal cancer, 99 lung cancer and 98 endometrial cancer) and 175 reference groups were tested for urine samples. The ANOVA analysis was used to compare the differences in the content of 10 OPFRs compounds in the urine of subjects of different ethnic groups. ROC curve analysis was used to determine the best decision value of whether the disease was present, and Chi-square verification was used to conduct disease risk assessment and verify the feasibility of the set reference value. Results The BCEP (6.23 ± 2.19 ng/mL) of most patients with hemodialysis, lung cancer and esophageal cancer was significantly higher than the reference group (0.89 ± 0.38 ng/mL). Patients with gynecological diseases had a higher BDCPP (4.29 ± 1.97 ng/mL) than the reference population (0.76 ± 0.32 ng/mL), which was consistent with the conclusions of previous animal experiments. Since it is not easy to explain the direct correlation between OPFRs and the disease. We decided to sum the detection values of 10 OPFRs. We found that their sum was greater than 2.05 ng/mL. The risk of infertility was 37.8 (95% CI: 11.07–129.14), the risk value of esophageal cancer was 83.3 (95% CI: 25.25–274.85) and the risk value of severe chronic kidney disease was 56.7 (95% CI: 17.49–183.97). Conclusion Due to the different types of OPFRs used in different countries, it is impossible to directly apply the reference values of other countries to their own people. So we develop the OPFRs detect method and verify the reference values through a series of analysis and discussion. Which will help us further understand the association between these environmental hormones and diseases.

Post-pubertal management of undescended testes from the malignancy risk point of view: a systematic review

Background: Undescended testes (UDT) is a condition where one or both testes is absent in the scrotum. The general age recommendation in which the treatment should be performed is before 18 months old due to the infertility risk and malignancy in later life. On the other hand, in post-pubertal UDT, the current guideline recommends orchiectomy; however, this recommendation is weak. Therefore, this study aimed to provide a systematic review of post-pubertal UDT treatment, focusing on the malignancy risk point of view. Methods: A systematic search was performed using PubMed, Wiley Online Library and the Cochrane Library up to 5 March 2023. Any study with either post-pubertal orchiectomy or orchidopexy in patients with UDT and reporting the testicular malignancy was included. The exclusion criteria were studies with lack of information of UDT correction time, no history of correction and the full text wasn’t available. The data collected were the occurrence of testicular malignancy in post-pubertal UDT patients corrected with any method. Quality and bias assessment was assessed with Newcastle-Ottawa scale and Joanna Briggs Institute tools. Results: Seven articles (three case reports and four observational studies) were reviewed with a total of 42 patients who underwent post-pubertal correction of either unilateral or bilateral UDT. The correction age ranged from 13 to 34 years old, with follow-up of 48.7–252 months. Among those who developed malignancies, the most common were seminoma, teratoma and carcinoma in situ of the testes. In addition, this study was able to propose an algorithm for post-pubertal UDT treatment strategy. Conclusions: The scarce resource was the main limitation of this study. Nevertheless, this review showed that post-pubertal UDT management should be tailored individually. Several factors that should be considered include the condition of the contralateral descended testis, UDT location, serum testosterone level, patient’s age, comorbidities, and interest in fertility.

Male infertility risk and gut microbiota: a Mendelian randomization study.

In recent decades, the decline of male sperm quality has become a worldwide phenomenon, with sperm quality of critical importance for the ability to conceive naturally. Recent studies suggest that male fertility function is closely linked to the gut microbiota, however, the cause-and-effect association between the gut microbiota and male infertility risk is currently unclear. We performed one two-sample Mendelian randomization (MR) study, which uses summary data on human gut microbiota from the MiBioGen consortium as factors of exposure. FinnGen Consortium R8 data was used to obtain GWAS data for male infertility. To evaluate cause-and-effect associations linking gut microbiota and male infertility risk with multiple Mendelian randomization methods, we included inverse variance weighted (IVW), MR-Egger, and Maximum Likelihood (ML) Ratio. The heterogeneity of instrumental variables was evaluated through Cochran's Q, Rucker's Q, and leave-one-out analysis methods. We found a positive association between Allisonella, Anaerotruncus, Barnesiella, Intestinibacter, and Lactococcus with male infertility risk according to the MR analysis results. Bacteroides Romboutsia, Ruminococcaceae (NK4A2140group), and Ruminococcaceae (UCG011) play a protective function in male infertility pathogenesis. It was found that gut microbiota and infertility are causally related in this study. In subsequent studies, there is a need to build a larger and more comprehensive GWAS database on male infertility, which will reveal the underlying mechanisms for gut microbiota and male infertility. There is a need for randomized controlled trials for validating the protective effect of the associated gut microbiota against male infertility risk, and for exploring the associated mechanisms.

Acute Large Ovarian Cyst After Surgical Resection of Juvenile Granulosa Cell Tumor Stage 1C.

Juvenile granulosa cell tumors (JGCTs) are rare, though carry significant burden of morbidity and mortality. A 15-year-old menstruating female with abdominal pain was diagnosed with a large 22.3cm pelvic mass. CA-125 and LDH were elevated. Exploratory laparotomy was undertaken due to lesion size, and left salpingo-oophorectomy with omentectomy was completed. Pathology confirmed JGCTs with focal disruption, consistent with Stage IC disease. Six weeks postoperatively, the patient experienced recurrent abdominal pain and ultrasound revealed a 7.9cm right ovarian cystic structure. Given size and nodularity, management was discussed with a multidisciplinary team. Serial ultrasounds demonstrated resolution of the cyst. Workup for ovarian masses in pediatric patients has added complexity of fertility preservation. Once ovarian torsion is ruled out, imaging and laboratory studies are completed to characterize the mass. In pediatric patients with cancer of the Mullerian structures and risk of infertility, decision-making can be challenging and is best managed with a multidisciplinary approach.