bluuebunny/crossref_metadata_2025 huggingface dataset:
#342 : Asherman’s Syndrome Attributed to Genital Tuberculosis: A Case Report
Authors: Yuad Haviz
Published: January 2024

Background: Asherman’s syndrome is a rare pathology secondary to intrauterine adhesion formation characterized by menstrual disorders and reproductive dysfunction. Although the cause intrauterine adhesion is thought to be associated with vigorous curettage or previous uterine surgery, other causes such as tuberculosis or schistosomiasis leading to intrauterine adhesion, are particularly important in developing countries.

Case Presentation: A 33-year-old, multiparous woman, has applied for care to our hospital after 6 months of secondary amenorrhea. Other than occasional untreated heavy vaginal discharge, she had no past medical history nor prior uterine surgical procedure. No one in her family was treated for tuberculosis. Previously she was given combination oral contraceptive pills for 2 months, with no desirable outcome. On June 2022, we conducted a transvaginal ultrasound, with several features suggestive of uterine synechiae i.e. interrupted endometrial line in sagittal plain, small focal cystic areas within endometrium, and hyperechoic lesion with and without posterior shadowing. We decided to perform a hysteroscopy, with findings of mottled endometrium across the fundus and corpus of the uterus. Adhesiolysis was performed. An intrauterine foley catheter was inserted to prevent the reformation of adhesions. The specimen from this procedure were collected for pathology testing, with positive result for endometrial tuberculosis with caseous necrosis. The patient was treated with anti-tuberculosis drugs for 9 months. Upon completion of her tuberculosis treatment, she received combination oral contraceptive pills for endometrial restoration. She had her first period on May 2022, but only scanty bleeding occurred. On July 2022, she had two days of period with heavier blood flow. She is still closely observed.

Conclusion: Asherman’s syndrome attributed to genital tuberculosis may emerge in otherwise healthy individual especially in countries where tuberculosis is prevalent. Although the results of hysteroscopic adhesiolysis in Asherman’s syndrome are encouraging, unfortunately, women with Asherman’s syndrome due to genital tuberculosis have poorer prognosis for restoration of menstrual function as there is usually complete destruction of endometrium by the mycobacterial disease. Well-designed clinical trials are needed to determine the most appropriate diagnostic and therapeutic modalities.
#61 : Frugal Exoscope: A Potential Option for Microsurgery and Training Program in Male Infertility in the Context of Emerging Markets
Authors: Khoa Le Dang , Hoang Le , Thang Le Duc , Trieu Vy Ngo Dinh , Dung Mai Ba Tien , Huy Duong Quang , Nhu Giang Huynh , Handelsmen David
Published: January 2024

Background and Aims: Conventional microscopes and exoscopes currently play pivotal roles in the microsurgery or training of male infertility. However, they are expensive and unaffordable in low resource settings which limits training or application of advanced methods. The study aimed to introduce a new, low–cost exoscope system and evaluate its frugal innovation.

Method: Using animal models, we evaluated a new frugal exoscope system (called DKTA) in experimental microsurgery of vas deferens repair. Five experts in male infertility surgery undertook an anonymous survey to elucidate their experience with DKTA system use. Three crucial criteria (i.e., substantial cost reduction, concentration on core functionalities, optimised performance level) were evaluated to determine whether the DKTA is effective as frugal innovation. The survey used a 5-point Likert scaling of responses to eight statements investigating surgical, ergonomic, and educational aspects.

Results: The DKTA system, including an optical microscope and ultrahigh definition camera (4K), was an exoscope placed between 20–40 cm from the surgical field. It was held in position with a camera support arm on casters and connected to a 65-inches smart TV. DKTA system met the three crucial criteria of frugal innovation, including substantial cost reduction, concentration on core functionalities, and optimised performance level. Five male infertility microsurgeons reported positive evaluations of the DKTA system (use modal scores) when performing experimental vasovasostomy.

Conclusions: DKTA system, a frugal innovation, has a valuable contribution to the training programme and performance of male infertility microsurgery in low–resource settings.

Acknowledgements: We want to send special thanks to the Centre for Training and Scientific Research staff, Tam Anh General Hospital for their logistics support.
#90 : Association of Serum Vitamin D Level with Asthenozoospermic Male
Authors: Ara Rowshan
Published: January 2024

Background and Aims: Vitamin D deficiency is one of the most common health problems throughout the world and has an effect on reproductive process. But there is conflicting data about potential association between serum vitamin D level and semen quality. Currently available data indicate that vitamin D has a vital role in sperm motility which is crucial for fertility. The aim was to evaluate the association of serum vitamin D level with asthenozoospermic male, a medical condition characterized by reduced sperm motility which can lead to male infertility.

Method: This cross-sectional analytic study was conducted on 314 men attending the Department of Reproductive Endocrinology and Infertility, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Considering the eligibility criteria all participants were categorized into two groups; Group-I: 157 asthenozoospermic male, Group-II: normozoospermic male, according to WHO ‘strict’ criteria 2010. Blood and semen samples were obtained for assessment, and data were adjusted for age, body mass index (BMI), total motility and progressive motility. Vitamin D levels were classified according to the Endocrine Society Guideline. Statistical analyses were carried out by using Statistical Package for Social Sciences version 22 for Windows.

Results: It was observed that mean vitamin D level was 16.63± 5.54 ng/ml in asthenozoospermic group and 19.83± 5.33 ng/ml in normozoospermic group. Mean vitamin D level was significantly (p<0.05) lower in asthenozoospermic group. It was noticed, 86.6% patients were vitamin D deficient (<20 ng/ml) in asthenozoospermic group compared to 56.7% in normozoospermic group. Low vitamin D is 5 times increased risk of developing asthenozoospermia at 95% CI (2.74-8.99). There was a positive significant correlation (r=0.285; p<0.001) between serum vitamin D level with total motility and progressive motility (r=0.232; p<0.001).

Conclusion: Study showed a significant association between low serum vitamin D level and Asthenozoospermia. But cross-sectional study makes it difficult to establish causal relationship. Hence, higher quality studies are required.
#97 : Can Platelet Rich Plasma (PRP) Improve Human Ejaculated Sperm Quality? A Systematic Review and Meta Analysis
Authors: Bofe Adelina Amelia Febriani , Dewanto Agung , Widad Shofwal , Chandra Lukman Ade
Published: January 2024

Background and Aims: Males are found contribute to 50% of infertility cases overall. Abnormal sperm parameters, such as low concentration, low motility, or abnormally morphology is thought to play a major role in male infertility. In many recent studies, Platelet Rich Plasma (PRP) was reported to have potential therapeutic effect. PRP with its rich growth factor composition, has already proven beneficial in regenerative therapy. PRP can improve the structural and functional impairment of the testis, thereby improve the sperm quality as its product. This study aims to identify the improvement of ejaculated sperm concentration, motility, morphology after treatment with PRP.

Methods: A systematic search was conducted in PubMed, Cochrane and Google Scholar databases up to November 2022. We used Prisma’s checklist 2020 as a guideline for writing this. To be included in this meta-analysis, eligible studies had to be a clinical trial comparing ejaculated sperm with PRP treatment and no PRP addition. We conducted both quantitative and qualitative analysis of the assessed outcomes.

Results: A total of 91 studies were retrieved. After excluding ineligible publication, 5 studies were finally included in the present meta-analysis (n=331). Among them, varied methods of PRP intervention, but all of them had using PRP 2%. By using a random effect model, there is an improvement of the progressive sperm in group with PRP treatment (MD 15,00, 95%-CI 6,71-23,29). Quantitative analysis (meta-analysis) was not carried out for sperm concentration and morphology, but was explained descriptively, that sperm concentration and morphology increased after PRP treatment. The articles included in the analysis have a low risk of bias.

Conclusions: There is an improvement in sperm progressivity after treatment with PRP, that also means there is an improvement in human ejaculated sperm quality. Although found beneficial enhancing the sperm progressivity, but still needed strong evidence for further research.
#108 : Methods of Sperm DNA Fragmentation (SDF) Testing and Interpretation: Results from the Global Andrology Forum Survey
Authors: Benny Paula , Huang Zhongwei , Sashidharan Shaili , Farkouh Ala’a , Shah Rupin , Agarwal Ashok
Published: January 2024

Background and Aims: Sperm DNA fragmentation (SDF) is caused by apoptosis, oxidative stress or incomplete chromatin maturation and can result in male infertility and poor reproductive outcomes. Despite growing trends, there are no specific recommendations on specific diagnostic tests used, assay cut-offs or abstinence periods prior to SDF testing. Therefore, we conducted a global survey to evaluate the approaches used to diagnose SDF, towards a consensus in the field of SDF research and clinical management.

Method: The survey collected cross-sectional global data from 55 countries following the CHERRIES protocol. 436 respondents included clinicians, researchers and reproductive biologists from academic, public and private health sectors, all of whom utilize SDF testing in their routine patient care and practice (Fig. 1).

Results: Survey results showed that TUNEL (28.6%), SCSA (24.1%), SCD (19.1%) and Comet (5.3%) were most frequently used to diagnose SD (Fig. 2A). Assays were chosen primarily due to their availability (70.0%), cost (44.05%) and accuracy (35.48%). Published evidence on assays (25.71%), training of staff (25.48%), cost to patients (21.67%), assay time (18.81%), ease of interpretation (18.33%) and performance (17.38%) were taken lesser into consideration when selecting SDF diagnostic tests (Fig. 2B). Assay cut-offs of “30% or higher” (33.7%) were most frequently used to diagnose SDF (Fig. 2C). Finally, an abstinence period of 3-5 days was mostly recommended (53.6%; Fig. 2D). The results of this survey provide valuable data on SDF assays used in clinical practice as well as factors affecting assay choices such as availability of resources, personnel and complexity in assay processing. As decreased abstinence period is associated with lower SDF, testing is recommended with an abstinence period of less than five days. We observed that there was a lack of standard cut-off values, and every laboratory should establish its own reference values based on predictive values for fertility outcomes.

Conclusion: We present new data associated with SDF testing in real-world practice, on a global scale. The trends and conclusions derived from the study are recommended for inclusion into the 6[Formula: see text] Edition WHO Manual, towards optimized patient care.
#126 : The Effect of Maternal Low Protein Diet on Sertoli Cell Population and Testicular Vacuoles in Male Offspring
Authors: Alfathdry Arsyad , Anshori Khoiruddin , Dewanto Agung , Gunanegara Rimonta F.
Published: January 2024

Background and Aims: Several studies have found that diet is critical during a female’s pregnancy. The nutritional condition of pregnant women can have long-term consequences for their children, particularly the growth of the reproductive system. However, previous studies have various opinions regarding whether or not the nutritional status of the maternal correlates with seminiferous tubule diameter and the Sertoli cell amount of their offspring. This study aims to observe the effect of low protein diet on pregnant mice towards the offspring’s seminiferous tubule diameter, Sertoli cell, and vacuole.

Method: Ten female ddY mice were split into two groups and given two months of treatment with either a normal protein diet (14%) or a low protein diet (10%). The mice were mated to produce offspring after treatment. Each group had five male progenies that were raised until they were three months old before being terminated to retrieve their testicles. Hematoxylin-eosin staining was used for histological analysis of the testicle sample. Testicles samples were observed for seminiferous tubule, Sertoli cell, and vacuole. Data was presented as mean & standard deviation. ANOVA and the Mann-Whitney U test was used to analyze the data. Statistical significance was accepted at p<0.05.

Results: There were no statistical differences between the offspring’s seminiferous tubule diameter and Sertoli cell count in the normal protein diet group and the low protein diet group (6.28±1.79 vs 6.47±0.79; 4.72±3.13 vs 4.84±2.81). On the contrary, the low protein diet group has a higher vacuole amount than the normal protein diet group (6.76±4.59 vs 3.64±3.07; P=0.004).

Conclusion: A maternal low-protein diet did not affect the Sertoli cell population or the length of the child’s seminiferous tubules but led to a significant increase in vacuoles.
#163 : Stress and Occupation Impair Male Fertility
Authors: Pangestu Mulyoto , Rahadyan Arkananta Imannuelito , Lestari Silvia W
Published: January 2024

Background and Aims: Jakarta is a metropolitan city of Indonesia and most people in Jakarta are working on various occupation such as technology-based and highly skilled occupations are common (construction workers, engineers, programmer, entrepreneurs) and desk-based workers. Those occupation, stress from those occupation and environment may impair male fertility. This study was aimed to determine specific occupations, occupational stress and environment and their association with sperm parameter.

Method: A descriptive cross-sectional study was used, and 24 male participants underwent IUI treatment in Yasmin Fertility Clinic, Jakarta were recruited. Sperm concentration, motility, morphology, velocity was analyzed using Computer Assisted Sperm Analysis (CASA) and sperm DNA fragmentation index was assessed using Sperm Chromatin Structure Assay (SCSA). Interview was also conducted to obtain information on age, length of marriage, biological children, occupational exposure, occupational-related psychological stress. The results were compared to parameter in WHO manual 6th edition.

Results: All 24 participants experienced exposure to potential disruptor to fertility such as vehicle emission, smoke inhalation and computer radiation (Fig. 1). Their raw semen parameters were lower compared to WHO manual 6th edition. Further results indicated that washing increased the value of all standard parameters and reduced sperm DNA fragmentation index in all samples. Further results showed abnormal morphology and sperm on fresh ejaculate are affected by stress intensity and frequency. However, total motility and abnormal morphology are significant correlated to stress intensity and frequency on both before and after sperm washing (Table 1).

Conclusion: Types of occupation and highly exposed to air pollution and/or demands prolonged time of sitting behaviour pose higher risk of sperm quality deterioration. Also, psychological stress resulted from workload may associate with sperm parameters outcome.
#227 : Is Sperm DNA Fragmentation Assay a Useful Predictor in ART Outcomes?
Authors: Chua Shiao Chuan , Yovich Steven John , Hinchliffe Peter Michael , Yovich John Lui
Published: January 2024

Background and Aims: The Sperm DNA Fragmentation (SDF) assay has been a promising tool for evaluation of male fertility in assisted reproductive technology (ART). Our primary aim is to assess the impact of SDF levels (<15% and ≥15%) on the laboratory and clinical outcomes; and secondary aim to evaluate those outcomes among 3 ART subgroups namely IVF–ICSI Split, IVF and ICSI cycles.

Method: This retrospective cohort study was conducted on 1148 males who presented along with their partners for infertility management at the PIVET Medical Centre between 2013 and 2022 and had their SDF assay performed by Halosperm. They undertook 1600 ART cycles with outcomes divided into 2 groups based on SDF levels <15% and ≥15%. Categorical data were analyzed by Chi-squared or Fisher’s exact test.

Results: The overall rates of fertilization, blastocyst development, good–quality blastocyst, clinical pregnancy, miscarriage and livebirth rates were comparable between the <15% and ≥15% SDF groups. Nevertheless, when comparing these outcomes according to female age groups, the clinical and livebirth rates were significantly higher in women <35 years in the SDF <15% (44.1%, p=0.04; 38.6%, p<0.01). Among the 3 ART modalities, the fertilization rates were optimised in both SDF groups by ICSI (75.5%, p<0.0001; 74.1%, p<0.0001), however ICSI also has the lowest blastocyst rate in both SDF groups (p<0.0001 and p<0.001). The IVF-ICSI Split modality generated the highest rate of good-quality blastocysts in both SDF groups <15% (44.9%, p<0.0001) and ≥15% (50.0%, p<0.001). Although the clinical pregnancies were not highest in the IVF modality, it carried the lowest miscarriage rate resulting in the highest live birth rate in SDF <15% group where the women were aged <40 years.

Conclusion: The SDF assay is predictive of clinical and livebirth rates for women aged <35 years. IVF is an effective modality among women aged <40 years where the SDF level is <15%.
#230 : The Effectiveness of Spermatid Injection (ROSI, ELSI) Versus Spermatozoa Injection (ICSI) in Infertility Treatment for Men with Non-Obstructive Azoospermia (NOA)
Authors: Tang Van , Thi Huyen Dang , Thai Loc Ly , Tien Dung Mai Ba , Dinh Hieu Le , Tanaka Atsushi , Diem Tuyet Hoang Thi , Van Thuan Nguyen
Published: January 2024

Background and Aims: About 1% of men suffer from azoospermia, a condition of having no sperm in the ejaculate. Non-obstructive azoospermia, which affects 60% of azoospermia patients, is the most severe form of male infertility and requires testicular sperm extraction for sperm retrieval. Despite a 50% success rate, if no mature sperm is found, NOA men have no choice become biological fathers. To overcome this, researchers have attempted to use spermatid injection techniques, such as round spermatid injection (ROSI) or elongating/elongated spermatid injection (ELSI), to give hope for pregnancy. Spermatids are immature sperm but contain a haploid genome as spermatozoa.

The aim of this prospective cohort study was to evaluate the effectiveness of ROSI and ELSI in cases where spermatozoa were unavailable.

Method: Ninety-nine men diagnosed with NOA were recruited for the study. When the male partners lack spermatozoa in the testicular biopsy but have normal good-looking spermatids, they are consulted to join in the research. The intervention group received ROSI and ELSI, while the control group received spermatozoa injection into oocytes (ICSI).

The primary outcome measures were fertilization, embryo development, clinical pregnancy, and live birth rate.

Results: The overall fertilization rate (2PN) per MII oocyte injected after ROSI was low at 31.0% compared to ELSI and ICSI at 67.7% and 77.2%, respectively. The pregnancy rate after ROSI was also low, with 3.3% per transferred cycle and 2.2% per embryo transferred. The pregnancy rate of ROSI was much lower than ELSI (42.9%) and ICSI (55.6%). Normal pregnancy and live birth resulted in three groups (Table 1).

Conclusion: ROSI and ELSI can be considered alternative methods of infertility treatment in cases where spermatozoa are unavailable.
#241 : Impact of Antioxidants in Improving Semen Parameters Like Count, Motility and DNA Fragmentation in Sub-Fertile Males: A Randomized, Double Blind, Placebo Controlled Clinical Trial
Authors: Patki Ameet
Published: January 2024

Background and Aims: Male infertilities are solely responsible for 20-30% of infertility cases. Oxidative damage of sperm DNA is positively linked with oligoasthenoteratozoospermia (OAT), and male infertility. The antioxidants are being explored worldwide to combat OAT, sperm DNA fragmentation and reactive oxygen species. The objective of the study was to assess the effectiveness of an antioxidant blend in improving sperm count, semen parameters and reducing DNA fragmentation index (DFI) in sub-fertile males.

Method: A prospective, double-blind, randomized, placebo-controlled trial was conducted in 300 sub-fertile males (25–45 years) from ten study sites in India. Subjects were randomized in either the antioxidant blend treatment group or placebo group. We assessed changes in sperm count, motility, normal morphology, semen volume, and percent DFI before and after treatment (90 days). To further stratify data on different criteria post hoc analysis was performed. Statistical analysis was performed using SPSS 10.0 software.

Results: There were improvements in sperm count, semen volume, sperm motility, and sperm normal morphology in the treatment group. There was improvement in sperm count in severe oligospermia subjects (sperm count < 5 million/mL, 5–10 million/mL, 10.1–15 million/mL), and high-extremely higher baseline DFI (20–30%, 31–40% and above 40%), as per post hoc analysis. There was no premature discontinuation and adverse events were reported during the study, indicating safety and well-tolerability of treatment.

Conclusion: Study results confirmed the well-researched fact of antioxidants being effective to reduce oxidative stress and thus improve sperm DNA integrity and also improved semen parameters particularly in males aged 40 and above.
#337 : Six Characters of Seminiferous Tubules Appearances During Micro-Tese Related with Different Sperm Retrieval Rate
Authors: Zhang Jing , Chen Hong , Zhao LuGang , Liu GuiHua , Liang XiaoYan , Fang Cong
Published: January 2024

Background and Aims: For non-obstructive azoospermia (NOA) patients, micro-TESE is considered to have higher sperm retrieval rate (SRR) than traditional surgery. However, various clinical parameters are not reliable predictors for the presence of focal spermatogenesis and SRR. This study summarized the characters of seminiferous tubules appearances and investigated their relationship with SRR.

Method: This was a retrospective study. From September 2014 to April 2023, 638 NOA patients treated with micro-TESE were divided into six groups according to the seminiferous tubules appearances (Group-A: homogeneously thick, Group-B: homogeneously thin, Group-C: seminiferous tubules were severe thin and loss the tubal appearance, Group-D: the testicles were filled with hyperplastic Leydig cells, seminiferous tubules were severe thin and rare, Group-E, thick tubules mixed with thin tubules, Group-F, extensive testicular microlithiasis). Age, testicular volume, serum FSH, testosterone level, SRR and the heterogeneous seminiferous tubules presenting rate (HSTPR) were compared.

Results: Sperms were successfully retrieved in 333 cases (SRR=52.2%). There were no statistical differences in age, testicular volume, FSH and testosterone level between the patients who succeeded and failed to obtain sperm (Table 1, all [Formula: see text]>0.05). The constituent ratio of etiology was different in the six groups (Table 2, [Formula: see text]<0.05). Between the six groups, testicular volume, FSH, testosterone, SRR and HSTPR were statistically different (Table 3, all [Formula: see text]<0.05).

Conclusion: Age, testicular volume, FSH and testosterone were insufficient to predict the SRR of NOA patients. Micro-TESE is commended to terminated when sperm are retrieved in case that the seminiferous tubules are rare or too thin to present tubal appearance, thick tubules mix with thin tubules or extensive testicular microlithiasis present (Group C-F). If the tubules appear homogeneously thick or thin, micro-TESE would has less advantage comparing with conventional multiple TESE because of the difficulty to identify the differences between the tubules even if the sperm is finally retrieved (Group A-B).
#338 : Insights into the Zona-Pellucida Mediated Selection of Fertilization-Competent Spermatozoa
Authors: Leung Erica Tsz Ying , Lee Chuk-Lun , Chiu Philip C.N.
Published: January 2024

Background and Aims: Human zona pellucida (ZP) selectively interacts with high-quality spermatozoa characterized by superior morphology and normal chromatin structure to achieve fertilization. Human ejaculate contains millions of spermatozoa with varying degrees of fertilization potential and genetic quality, of which only thousands of motile spermatozoa can bind to the ZP at the fertilization site. However, direct evidence for ZP-mediated sperm selection process is lacking. This study aims to demonstrate that spermatozoa-ZP interaction represents a crucial step in selecting fertilization-competent spermatozoa in humans.

Method: Human spermatozoa and oocytes were obtained with written consents from the donors attending our assisted reproduction program. Acrosome intact, ZP-bound and unbound spermatozoa were recovered using the modified spermatozoa-ZP coincubation assays. ZP-binding protein expression on ZP-bound and unbound spermatozoa were examined by immunofluorescence staining. And the genetic integrity and epigenetic landscapes were evaluated by TUNEL assay, COMET assay, acridine orange staining, chromomycin A3, and immunofluorescence staining for 5-methylcytosine.

Results: The time course data demonstrated that ZP interacted with a small proportion of motile spermatozoa. Heat shock 70 kDa protein 2 (HSPA2) and sperm acrosome associated 3 (SPACA 3) are two protein markers associated with the sperm ZP-binding ability. ZP-bound spermatozoa had a higher percentage of positive HSPA2 (85.8% vs. 45.9%, p<0.05) and SPACA3 signals (86.3% vs. 30.5%, p<0.05) than the unbound ones. The signal intensities of both markers were stronger in the ZP-bound spermatozoa than the unbound ones. ZP-bound spermatozoa had a significantly higher level of normal morphology, DNA integrity, chromatin integrity, protamination and global methylation when compared to the unbound ones.

Conclusion: Our results validated the functional role of spermatozoa-ZP interaction in providing diagnostic information regarding the fertilization potential and genetic qualities of spermatozoa independent of those derived from the standard semen analysis.
#363 : Kisspeptins and Human Reproduction: New Challenges in the Management of Couple Infertility
Authors: Sellami Afifa , Daoud Salima , Abdelkafi Olfa , Amor Maroua Ben , Moalla Faradis , Rebai Tarak
Published: January 2024

Background and Aims: Human reproduction is strictly controlled by a complex neurohormonal system including the gonadotropin-releasing hormone (GnRH) production, which stimulates anterior pituitary gonadotropes secretion and thereby gonadal function. Now, it is well known that GnRH neurons are regulated by Kisspeptins, a family of neuropeptides encoded by the Kiss1 gene and produced mainly in the arcuate and periventricular nuclei of the third ventricle in the hypothalamus. This review aims to provide an updated view in the physiological effects of kisspeptins in male and female reproduction and to highlight future research challenges in therapeutic alternatives for the management of couple infertility.

Method: A non-systematic review of the literature was performed by screening PubMed up to April 2023 using the search terms including “Kisspeptin”, “gonadotropin-releasing hormone”, “male infertility”, “female infertility”, “sperm”, “oocyte”, and “Assisted Reproductive Technology”.

Results: Many reports suggested the importance of kisspeptins in various aspects of male and female reproduction, from sexual differentiation and puberty onset to adult regulation of gonadotropin secretion and the metabolic control of fertility. Kisspeptin is involved in oocyte development, quality of semen, steroidogenesis in both the ovaries and testes, sexual desires and pregnancy.

Recently, a potential clinical relevance of kisspeptins was noted with emerging interests in applied medicine. Some investigations are being carried out to develop these neuromodulators as a diagnostic marker in male and female infertility. Kisspeptin analogs could constitute a new therapeutic strategy based on hormonal manipulation of the hypothalamic-pituitary-gonadal axis.

Conclusion: Further clinical trials are needed to provide the required evidence for the use of kisspeptin to trigger reproductive axis, gonadic functions and gametes differentiation guiding future clinical practice in couple infertility.
#229 : The Impact of Menopausal Phase to Depression
Authors: Jatiningtyas Abida Zuhra , Alaydrus Syecha Tsania , Nugroho Christa Edo , Melinawati Eriana , Budihastuti Uki Retno , Laqif Abdurahman , Wijayanti Agung Sari
Published: January 2024

Background and Aims: In premenopausal and menopause women, a woman will start to experience mood problem and in more severe cases can cause depression. Researchers have connected the relation between hormonal changes that occur with the emersion of the symptom. In Indonesia, the awareness of the community to check themselves due to mental disorders is still quite low. This leaves many cases of depression have not been revealed. The main objective of this study was to find out the relation of menopause and depression by evaluating the subjects result of Hamilton Depression Rating Scale (HAM-D).

Method: This research used thematic analysis of semi-structured interview based on Hamilton Depression Rating Scale (HAM-D). The collected data were analysed using IBM SPSS Statistic 23.0 for windows. The populations in this study are all women aged between 40-60 years, totaling 60 people. The choosing of the patients based on some criteria: 1) the data was taken from women aged 40 and above; 2) showing symptoms of premenopausal or menopause; 3) The researcher did not consider patient’s history of depression and other mental disorder; 4) That person have agreed to the informed consent.

Results: Measurements Hamilton Depression Rating Scale (HAM-D) classified someone as suffering severe depression disorder if the test score is 24 and above, moderate depression if the score between 17-23, mild depression score is 8-16, and normal if the score is below 8. The statistically significant score is set up at p <0.05 if there is correlation between menopausal and depression. Women experiencing menopause tend to tend to experience depression; (Correlation Coefficient = 0.176); (p=0.179 or p>0.05) compared to those of women without menopause or premenopausal.

Conclusion: The changes into menopausal phase increase the risk of being depressed even though it is low.
#370 : Hormone Replacement Therapy and Risk of Cardiovascular Diseases in Postmenopausal Women Aged 50-59 Years: A Systematic Review of Randomized Controlled Trials
Authors: Sutanto Reynardi Larope , Sugiyanto Michael , Wiweko Budi
Published: January 2024

Background and Aims: Cardiovascular diseases are the leading cause of mortality worldwide. Due to declining estrogen levels, women are at higher risk of contracting cardiovascular diseases. Although hormone replacement therapy (HRT) has the potential to prevent cardiovascular diseases, its safety and efficacy are still controversial. The window of opportunity theory suggests that initiating HRT during the early stages of menopause could have the most significant benefits. This review aims to assess available evidence on the effects of HRT in preventing cardiovascular disease in early postmenopausal women aged 50-59 years old.

Method: Systematic literature searching was conducted on four databases: Pubmed, EMBASE, EBSCOhost, and ProQuest. Using previously designed keywords, we searched for randomized controlled trials assessing the association between HRT and various cardiovascular outcomes. Critical appraisal was conducted using the Cochrane Risk of Bias 2.0.

Results: Six post-interventional analyses from 2 randomized controlled trials with a total of 9,838 subjects were included. The review only assessed the data from subjects aged 50-59 years old without any known comorbidities. Despite varying statistical significance among studies, we observed a relatively consistent trend that estrogen-only HRT lowers the risk of cardiovascular events, thus supporting the window of opportunity theory. However, there was also an increase in the risk of cardiovascular events in estrogen-progesterone combination compared to placebo or estrogen-only HRT.

Conclusion: By taking into account aspects of patient characteristics, age during first administration, regimens, and therapy duration, hormone replacement therapy has the potential to prevent cardiovascular diseases in early postmenopausal women aged 50-59 years old.
#285 : Amphiregulin Increases Pentraxin 3 Production via the EGFR-Mediated Erk1/2 Signaling in Human Granulosa Cells
Authors: Chang Hsun-Ming
Published: January 2024

Background and Aims: Pentraxin 3 (PTX3) plays a key role in the assembly of the extracellular matrix, which is critical for cumulus expansion, ovulation, and in vivo fertilization. As a member of the epidermal growth factor family, amphiregulin (AREG) mediates luteinizing hormone (LH)-induced oocyte maturation and cumulus expansion in mammalian follicles. The aim of this study was to investigate whether AREG regulates the expression and production of PTX3 in human granulosa cells and to examine its underlying molecular determinants.

Method: Immortalized human granulosa cells (SVOG cells) and primary human granulosa-lutein (hGL) cells obtained from women undergoing in vitro fertilization in an academic research center were used as the study models. The expression and accumulated levels of PTX3 were examined following cell incubation with AREG at different time points using the RT-qPCR and ELISA, respectively. Two kinase inhibitors (AG1478, and U0126) and small interfering RNAs targeting EGF receptor (EGFR) were used to verify the specificity of the effects and to investigate the molecular mechanisms. The results were analyzed by one-way analysis of variance.

Results: The results showed that AREG upregulated the expression and production of PTX3 in primary and immortalized hGL cells. Additionally, using a dual inhibition approach (kinase inhibitors and siRNA-based expression knockdown), we demonstrated that this effect was mainly mediated by the EGFR receptor. Furthermore, we revealed that the Erk1/2 signaling is the downstream signaling pathway that mediates the increase in PTX expression and production in response to AREG treatment in hGL cells.

Conclusion: AREG upregulated the expression of PTX3, leading to increased production of PTX3 in hGL cells. The AREG-induced cellular activities were most likely driven by the EGFR-mediated Erk1/2-dependent signaling pathway. Our findings shed light on the detailed molecular mechanisms by which AREG regulates the process of cumulus expansion and subsequent ovulation in humans.
#43 : Expression of miRNA-21-3p in Polycystic Ovary Syndrome and its Related Functions
Authors: Zhang Guoqing , Mukhri B. Hamdan , Zheng Lianwen
Published: January 2024

Background and Aims: PCOS is an endocrine-related disease related to abnormal folliculogenesis and is a leading cause of infertility worldwide. Inhibition of GCs proliferation and increased GCs apoptosis have been identified as the major factors in aberrant follicle maturation. Recently, the roles of miRNAs were identified in polycystic ovary syndrome (PCOS). For instance, miR-21-3p was identified as an important miRNA regulating autophagy of BGCs. Besides, studies showed that AMSC-EXOs can rescue the polycystic phenotype and metabolic dysfunction in PCOS ovaries by transferring miR-21-5p to the livers of rats with PCOS, finally improve reproduction. However, there is no research clarified the association between miRNA-21-3p and GCs function to date.

Method: In the present study, letrozole was used to establish the PCOS rat model. Separate the ovary and then miRNA-21-3p expression will be analyzed by RT-PCR. Primary rat ovarian GCs were isolated and incubated and transfected with mimic or inhibitor of miRNA-21-3p, CCK8 kit was used to detect cell viability, PR-PCR was used to detect cell proliferation and apoptosis related gene expression. Finally, flowcytometry was used to test apoptosis rate of Gcs.

Results: The expression of miR-21-3p in the ovaries of PCOS rats was significantly increased compared with that in control rats. Primary rat ovarian GCs were isolated and incubated successfully, and then CCK-8 experiment showed that GCs viability was significantly decreased when miR-21-3p was overexpressed. Additionally, the miR-21-3p mimic significantly decreased the expression of PCNA, Bcl-2, cell cycle-related genes (CDK2, CCNE1) and increased the expression of Bax and caspase3 in primary rat ovarian GCs. By contrast, transfected primary rat ovarian GCs using the miR-21-3p inhibitor significantly upregulated the expression of PCNA, Bcl-2, cell cycle-regulated genes (CDK2, CCNE1) and reduced the expression of Bax and caspase3. Finally, flow cytometry analysis demonstrated that overexpression of miR-21-3p significantly increased the apoptosis rate of GCs. By contrast, the suppression of miR-21-3p resulted in a significant decrease in the apoptosis rate of GCs.

Conclusion: In PCOS rat model, miRNA-21-3p was proved significantly increased compared with that in control rats. Which is participant in the development of PCOS by regulating the function of granular cells.
#109 : Differential Effects of Age and Lifestyle on Anti-Mullerian Hormone Levels and Ovarian Reserve in Asian Women with and Without Polycystic Ovarian Syndrome (PCOS)
Authors: Huang Zhongwei , Yang Qian , Lee Jovin , Benny Paula
Published: January 2024

Background and Aims: Polycystic ovarian syndrome (PCOS) afflicts 4-20% of all women at reproductive age and is a common cause of infertility. Elevated anti-Mullerian hormone levels (AMH), a clinical marker for ovarian reserve, are routinely associated with PCOS, however, an exact cut-off value has remained elusive. Interestingly, observational studies reported that women with PCOS have purported higher ovarian reserves, implied from higher AMH levels, and later age of menopause delayed by 2 years when compared to women without PCOS. Our study focuses on the Asian population, a demographic frequently under-represented in cohort studies. We posit that our results will bridge the gap in the collective understanding of PCOS and how age and lifestyle effects on ovarian reserves in Asian women.

Method: A large retrospective study was conducted at a tertiary-care hospital in Singapore from 2016-2020. AMH and clinical demographics from 3,739 Asian women aged 21-53 years were collected. Wilcoxon Rank Sum was used to analyze the data and significance was established if p<0.05. Logistic regression and ROC were generated in R.

Results: AMH (aOR=1.07), age (aOR=0.89) and BMI (aOR=1.12) were significantly associated with PCOS(p<0.001) in Asian women. AMH declined with age but the decline in the PCOS group was less severe, with 80% AMH retained in women in their 40s, as compared to controls which retained only 40% AMH(Fig. 1). BMI>25 and smoking status affected AMH levels with higher BMI and smoking associated with lower AMH. An ethnic stratification revealed that average AMH levels of Malay women with PCOS were lower than Chinese and Indian women in each age group (Fig. 2). The constructed model incorporating all variables had an ROC AUC=0.89.

Conclusion: This study highlights the importance of improving the resolution of PCOS diagnosis through AMH profiling, especially in Asian populations. The results from this study suggest potential beneficial effects of lifestyle modifications such as maintaining a healthy BMI and stopping smoking, especially in Asian women with PCOS.
#140 : Combined Use of Letrozole, Cabergoline and GnRH Antagonist to Prevent Ovarian Hyperstimulation Syndrome Completely in Polycystic Ovarian Syndrome Treatment
Authors: Yanagihara Yasuho , Ohno Motoharu , Kuwazuru Tomoichiro , Nakajima Daisuke , Nagayoshi Motoi , Tanaka Izumi , Tanaka Atsushi , Itakura Atsuo
Published: January 2024

Background and Aims: The main difficulty to treat polycystic ovarian syndrome (PCOS) is the possibility of ovarian hyperstimulation syndrome (OHSS). There are several clinical approaches to avoid dangerous complications of OHSS: laparoscopic ovarian drilling (LOD), in vitro maturation (IVM), and GnRH antagonist-GnRH agonist based controlled ovarian stimulation (COS) with low dose of gonadotrophin. However, clinical outcomes after using these methods are less satisfactory than COS in normal ovarian function. We started a new approach combining the use of three kinds of medicine, Letrozole, Cabergoline and GnRH antagonist from just after the oocyte pick up and continue for five consecutive days to prevent the occurrence of OHSS in the PCOS treatment.

Method: We compared the severity of OHSS after using a new treatment (the novel COS) in 53 women (55 cycles) with the severity of OHSS in a group of 37 women (37 cycles) who received the most widely used conventional GnRH antagonist-GnRH agonist- based COS for PCOS in retrospective cohort study.

Results: This table shows the comparison of clinical outcomes between two groups.

Conclusion: PCOS patients have been treated with hypostimulation methods and IVM to prevent OHSS. However, our method is considered to be more effective, safer and more versatile than any other treatment method. It seems to be an important alternative treatment method for PCOS patients. We believe this new treatment is highly recommended for the complete prevention of OHSS.
#226 : Comparison of Letrozole vs Letrozole Plus Metformin as First Line Ovulation Induction Drug for Infertile PCOS Women
Authors: Kar Sujata , Maharana Lipika
Published: January 2024

Background: Letrozole is currently considered as first line ovulation induction drug in anovulatory PCOS women. Insulin sensitizers like Metformin have a proven role as an adjuvant to improve ovulatory function in resistant PCOS women. Letrozole and Metformin combined as first line ovulation induction option has not been studied much, neither has been compared to other options.

Objective: The aim of this study was to compare Letrozole plus Metformin vs Letrozole alone as first line ovulation induction drug in treatment naive infertile PCOS women.

Materials & Methods: 125 PCOS patients with anovulatory infertility were randomized by a computer generated randomization list to receive either Letrozole 5 mg from day 3-7 of menses plus Metformin daily (65 patients,150 cycles, Group I) or Letrozole 5mg/day from day 3-7 (60 patients, 121 cycles, Group II). The primary outcome studied was live birth rates and the secondary outcomes reported were ovulation rate, mono / multifollicular development, endometrial thickness, pregnancy rates, abortion and twinning rates.

Results: Live birth rate was 33.8% in group I and 45.8% in group II (p=0.17) which was not statistically significantly different. The ovaluation rate was 85.9% and 86.7% (P=0.85) respectively. Multi follicular ovulation was slightly more in Group 2 (38.6% vs 48.1%).

Conclusion: There was no significant benefit of adding Metformin to Letrozole as first line ovulation induction drug in terms of live birth rate or ovulation rates.
#234 : Impact of Visceral Adiposity Index on the Pregnancy Outcomes of Women with Polycystic Ovary Syndrome
Authors: Nguyen Thanh Nam , Ho N A Vu , Nguyen L Duy , Nguyen H N Minh , Pham D Toan , Ly D Luong , Tran T N Mai , Ho M Tuong , Vuong N Lan
Published: January 2024

Background and Aims: Despite the widely used of body mass index (BMI) to indicate body fatness, it does not take into account muscle mass, bone density, overall body composition, and racial and sex differences. Visceral adiposity index (VAI) is an empirical-mathematical model gender-specific to indicate fat distribution and function. VAI was calculated based on simple anthropometry and metabolic parameters. There may be a correlation between VAI and reproductive outcomes. This study investigates the correlation between VAI and pregnancy outcomes in PCOS women.

Method: This prospective cohort study was conducted at IVFMD, My Duc Hospital, from June 2020 to August 2022. This study included infertile PCOS women aged between 18 and 40 years. At the initial workup, PCOS women were evaluated for their VAI. We then classified them into four groups based on their VAI: <1.5, 1.5-<3.0, 3.0-<4.5, and ≥4.5. We continued to follow their reproductive outcomes for up to 12 months since the initial evaluation. The primary outcome was the pregnancy rate 12 months after the first workup. Secondary outcomes were insulin resistance, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), pre-diabetes, and type 2 diabetes mellitus (T2DM).

Results: A total of 1,200 PCOS women were included in this study; of which, only 794 patients had complete data after 12-month follow-up. The mean age of patients was 29.2 ± 3.7 years. Mean BMI was 23.0 ± 4.0 kg/m2. Median VAI was 2.1 [1.3; 3.8]. Ongoing pregnancy rate was significantly lower in groups of women with higher VAI (47.9% in group with VAI of <1.5, 40.2% in 1.5-<3.0, 38.5% in 3.0-<4.5, and 33.9% in ≥4.5, respectively, P = 0.04). In addition, insulin resistance, IFG, IGT, and T2DM were found to be higher with increased VAI except for pre-diabetes.

Conclusion: VAI has a negative impact on ongoing pregnancy and is associated with an increased risk of glucose metabolic abnormalities in infertile women with PCOS. Clinicians may use VAI as a predictor of pregnancy outcomes and GDM to advise these patients on their pregnancy care.