Hrev_master Healthcare in Low-resource Settings 2024; volume 12:11985 Analysis of determinants of infertility among women at in vitro fertilization clinic in Surabaya Yati Isnaini Safitri,1 Esty Puji Rahayu,1 Lailatul Khusnul Rizki,1 Siska Nurul Abidah,1 Ima Nadatien2 1Department of Midwifery, Faculty of Nursing and Midwifery, Universitas Nahdlatul Ulama Surabaya; 2Department of Nursing, Faculty of Nursing and Midwifery, Universitas Nahdlatul Ulama Surabaya, Indonesia Abstract In social life and global health, infertility is common. History of abdominal surgery, body mass index (BMI), endometriosis, menstrual history, and polycystic ovarian syndrome (PCOS) have not been fully explained as female infertility factors. This study examined infertility causes at ASHA in vitro fertilization Primasatya Husada Citra (PHC) Hospital Surabaya. This quantita- tive study was cross-sectional. In May-July 2023, 82 childbearing- age women with infertility issues visited the hospital and complet- ed questionnaires. Description and analysis were performed using the Wilcoxon rank test to evaluate menstrual history, BMI, PCOS, endometriosis, and abdominal surgery history in relation to infer- tility. Infertility was statistically associated with abdominal surgery history (P=0.008), BMI (P=0.000), endometriosis diagno- sis (P=0.000), and PCOS (P=0.000). Women with abdominal surgery, endometriosis, and PCOS had significant infertility. Women’s infertility can be caused by ovulation disorders, tubal and pelvic disorders, or uterine disorders, but one-third of cases are unexplained. Infertility treatment may benefit from addressing abdominal surgery history, BMI, endometriosis, and PCOS. Early intervention and targeted care based on these determinants may improve fertility outcomes and reduce unexplained infertility. Introduction Infertility significantly impacts the psychology of married couples, causing feelings of depression, worry, and guilt. It also affects their social lives, making them reluctant to engage with others, yet it does not deter them from maintaining their house- hold.1,2 The incidence of primary infertility is 62%, while sec- ondary infertility, defined as the inability to have or maintain a pregnancy, stands at 38%.2 Research shows that 10-15% of the 39.8 million couples in Indonesia experience infertility, with 4-6 million couples requiring treatment to conceive.3 Basic health research data from 2018 indicates a rise in overweight (13.6%) and obesity (21.8%) among adults, correlating with a 31% increase in central obesity in those over 15 years old.4 The stress related to infertility negatively affects the quality of life, with fam- ily coherence mediating this stress impact.5 Infertility necessitates medical attention and treatment and is a significant life event affecting personal, relational, and social dimensions.6 It reveals intense stress and psychological vulnera- bility, sometimes leading to decreased marital satisfaction and family estrangement.7 Causes of female infertility are classified into ovulation disorders [e.g., polycystic ovarian syndrome (PCOS), menstrual cycle disorders, primary ovarian insufficien- cy], tubal and pelvic disorders, and uterine disorders (e.g., submu- Correspondence: Yati Isnaini Safitri, Department of Midwifery, Faculty of Nursing and Midwifery, Universitas Nahdlatul Ulama Surabaya, Surabaya, Indonesia. E-mail: yati@unusa.ac.id Key words: abdominal surgery; BMI; endometriosis; infertility; PCOS. Contributions: YIS, data curation; YIS, EPR, LKR, conceptualization, validation, writing – original draft; YIS, LKR, formal analysis; EPR, IN, investigation; IN, resources; YIS, EPR, LKR, SNA, methodology; YIS, SNA, visualization and writing. All the authors participated in the review and editing and approved the final version to be published. Conflict of interest: the authors declare no potential conflict of interest. Funding: this study was fully funded by the Institute of Research and Community Services (LPPM), Universitas Nahdlatul Ulama Surabaya with contract number: 570.206/UNUSA-LPPM/Adm-I/IV/2023. Ethics approval and consent to participate: the research procedure received an ethical letter from the Health Research Ethics Committee at Nahdlatul Ulama University, Surabaya No. 0274/EC/KEPK/UNUSA/ 2023. During the research, the researcher paid attention to the ethical principles of information to consent, respect for human rights, benefi- cence, and non-maleficence. Availability of data and materials: all data generated or analyzed during this study are included in this published article. Informed consent: written informed consent was obtained for anonymized patient information to be published in this article. Acknowledgments: we would like to thank Prof. Dr. Ir. Achmad Jazidie, M. Eng, as Chancellor of Universitas Nahdlatul Ulama Surabaya. Dr. Khamida, S. Kep. Ns., M. Kep as Dean of the Faculty of Nursing and Midwifery, Universitas Nahdlatul Ulama Surabaya. Nanik Handayani, S. Kep. Ns., M. Kes as Chair of the Midwife Professional Education Study Program. Achmad Syafiuddin S. Si., M. Phil., PHD as Chair of the Research Institutions and Community Service of Universitas Nahdlatul Ulama Surabaya. Dr. Amang Surya SpOG. as Leader of ASHA IVF Surabaya PHC Hospital. Intan Kusuma Hadie, and Endang Larasati as research enumerators. UNUSA academic community and all respondents who participated in this study. Also, we would like to acknowledge the contribution of the mentoring program conducted by the Research Centre of Excellence in Advancing Community Health, Surabaya, Indonesia. Received: 15 October 2023. Accepted: 30 May 2024. Early access: 1 July 2024. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2024 Licensee PAGEPress, Italy Healthcare in Low-resource Settings 2024; 12:11985 doi:10.4081/hls.2024.11985 Publisher's note: all claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organi- zations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. [Healthcare in Low-resource Settings 2024;12:11985] [page 513] Non -co mmerc ial us e o nly cous myoma, endometrial polyps, leiomyomas, Asherman’s syn- drome).8,9 Factors contributing to infertility include occupational factors (e.g., shift work, stress, radiation, chemicals), lifestyle fac- tors (e.g., age, nutrition, exercise, obesity, psychological stress, smoking, alcohol consumption), and environmental pollution.10-13 Smoking and alcohol consumption also significantly impact male reproduction.7,14,15 Hormonal changes due to PCOS, such as increased luteinizing hormones and progesterone levels, are linked with higher body mass index (BMI), increasing the risk of PCOS.16 Despite its status as a global health issue, research has not fully explained determi- nants of infertility like menstrual history, BMI, PCOS, endometrio- sis, and history of abdominal surgery. This study aimed to analyze the determinant factors causing infertility at ASHA in vitro fertil- ization (IVF) Primasatya Husada Citra (PHC) Hospital Surabaya. Materials and Methods Research design The research design employed was a quantitative descriptive study with a cross-sectional approach. This research aimed to ana- lyze the determinant factors causing infertility (menstrual history, BMI, PCOS, endometriosis, history of abdominal surgery) at ASHA IVF at PHC Hospital Surabaya. Study participants The sample consisted of all new patients of childbearing age (17-49 years) who experienced infertility problems. These patients were visited from May to July 2023, totaling 82 respondents selected using a simple random sampling technique. The respon- dents were women of childbearing age with infertility problems, and their names were medically registered at the ASHA IVF PHC Hospital. Data was obtained directly through interviews and ques- tionnaires diagnosing the causes of infertility experienced by respondents. Variable, instrument and data collection Independent variables included factors influencing infertility (history of abdominal surgery, BMI, endometriosis, menstrual his- tory, PCOS). The dependent variable was the infertility rate. The research instrument was a questionnaire developed by the authors containing questions on general data (age, height, weight to deter- mine BMI, categorized as underweight, normal, overweight, and obesity) and specific data (menstrual history measured as regular or irregular, PCOS, uterine endometriosis, history of abdominal surgery, and diagnosis of the cause of infertility). This data was obtained from secondary sources such as medical resumes. Data tabulation and analysis were conducted after collection. Data analysis The analysis aimed to determine the determinant factors (men- strual history, BMI, PCOS, endometriosis, history of abdominal surgery) causing infertility at ASHA IVF PHC Surabaya Hospital using the Wilcoxon rank test (P<0.05). Ethical clearance The research procedure received an ethical approval letter from the Health Research Ethics Committee at Nahdlatul Ulama University, Surabaya (No. 0274/EC/KEPK/UNUSA/2023). During the research, the researcher adhered to ethical principles including informed consent, respect for human rights, beneficence, and non-maleficence. Transforming Healthcare in Low-Resource Settings: A Multidisciplinary Approach Towards Sustainable Solutions Table 1. Distribution of respondents by characteristics (N=82). Characteristics Data distribution Frequency % Age group Late teens (17-25 years) 1 1.2 Early adulthood (26-35 years) 49 59.8 Late adult (36-45 years) 31 37.8 Early elderly (46-55 years) 1 1.2 History of abdominal surgery Has a history of abdominal surgery 37 45.1 No history of abdominal surgery 45 54.9 Menstrual cycle Regular 63 76.8 Irregular 19 23.2 Menstrual pain No pain 21 25.6 Light 24 29.3 Currently 14 17.1 Heavy 23 28.0 BMI Less 2 2.4 Normal 44 53.7 Overweight 23 28.0 Obesity 13 15.9 Diagnosis Endometriosis 22 26.8 Uterine myoma 5 6.1 PCOS 17 20.7 POF 5 6.1 Endometrial polyp 8 9.8 Adenomyosis 3 3.7 Tuba non-paten 6 7.3 Obesity 1 1.2 Hydrosalpinx 4 4.9 An explanation 10 12.2 Uterus bicorne 1 1.2 BMI, body mass index; PCOS, polycystic ovarian syndrome; POF, premature ovarian failure. Table 2. Statistical test result. Statistical testa Infertile – Infertile – Infertile – Infertile – Infertile – history of menstrual cycle BMI diagnosis menstrual abdominal pain levels surgery -2.661b -1.067c -7.057b -6.611b -1.384b p 0.008 0.286 0.000 0.000 0.166 BMI, body mass index; aWilcoxon signed ranks test; bbased on positive ranks; cbased on negative ranks. [page 514] [Healthcare in Low-resource Settings 2024;12:11985] Non -co mmerc ial us e o nly Results There were 82 respondents in this research, selected using the simple random sampling method. Table 1 shows that the character- istics of women in this study according to age reveal that the majority (59.8%) were in early adulthood (26-35 years). Regarding the history of abdominal surgery, the majority (54.9%) had no his- tory of abdominal surgery. Based on the menstrual cycle, the majority (76.8%) of women had regular cycles. According to com- plaints of menstrual pain, almost a third of the respondents (29.3%) experienced mild pain. Respondent characteristics based on BMI results showed that most women (53.7%) had a normal BMI. The diagnosis results indicated that some female respondents (26.8%) had endometriosis and others (20.7%) had PCOS. Based on the Wilcoxon signed-rank test results in Table 2, sev- eral factors influence infertility, including a history of abdominal surgery (P=0.008), BMI (P=0.000), a diagnosis of endometriosis (P=0.000), and a diagnosis of PCOS (P=0.000). In contrast, factors that do not affect infertility are the menstrual cycle (P=0.286) and the level of menstrual pain (P=0.166). Discussion Most respondents fall within the early adulthood age range (26-35 years), comprising 49 individuals (59.8%). Age significant- ly influences both male and female fertility, with women’s age being the primary determinant of conception and healthy pregnan- cies. While infertility can stem from various factors, it often involves contributions from both partners. Multivariate regression analysis has identified women’s age, duration of marriage, and socioeconomic status as predictive factors for reduced reproduc- tive opportunities in cases of secondary infertility.17 The incidence of infertility increases with age, particularly due to diminished egg quality in older women.18 Research by Dewi et al. revealed that a significant portion of couples seeking fertility treatments had hus- bands over 35 years old and wives aged 20-35 years, highlighting the importance of female age in fertility treatments. Several fac- tors, including the woman’s age, significantly influence the suc- cess of IVF procedures.19 Respondent characteristics based on BMI results showed that the majority of women (53.7%) had a normal BMI. Dag and Dilbaz highlighted the association between overweight and obesity in women of reproductive age and anovulatory infertility.10 In America, approximately 25% of cases of anovulatory infertility are attributed to being overweight. BMI serves as a straightforward tool for monitoring adult nutritional status, particularly in relation to being underweight or overweight.20 BMI is calculated by divid- ing a person’s weight in kilograms by their height in meters squared (kg/m2). However, the relative risk of anovulation increas- es significantly in women with BMI values of 24-31 kg/m2 and >32 kg/m2 compared to women with normal weight.21 Obesity induces three changes that disrupt normal ovulation, which can be corrected through weight loss. Despite having a normal BMI, women still face the risk of primary and secondary infertility, indi- cating the influence of factors beyond BMI on infertility.21,22 Women diagnosed with endometriosis in this study exhibit a significant association with infertility, as indicated by a P-value of 0.000. Endometriosis, a prevalent condition among women of childbearing age in this study, involves the abnormal growth of endometrial glands and stroma outside the uterus, often forming what is known as a chocolate cyst in the ovaries.23 Symptoms may vary, with women experiencing severe pelvic pain even in mild cases, while those with severe endometriosis may exhibit milder symptoms such as dysmenorrhea and dyspareunia.24 Other symp- toms include abnormal uterine bleeding and infertility, both prima- ry and secondary. Internal examinations may reveal small lumps in the sacro uterine ligament and a retroflexed uterus or adnexa that are difficult to move. Endometriosis, traditionally defined as the presence of endometrial tissue outside the uterus, has been recog- nized as a painful condition often requiring surgical intervention.25 This study found that 26.8% of respondents were diagnosed with endometriosis, which significantly impacts fertility, with 30-50% of affected women experiencing infertility. Untreated endometrio- sis reduces the likelihood of conception compared to the general population, and even mild cases are associated with decreased pregnancy rates compared to unexplained fertility24. Studies on IVF suggest that advanced endometriosis is linked to poor ovarian reserve, low oocyte and embryo quality, and compromised implan- tation rates.26,27 Women diagnosed with PCOS account for 20.7% of all respon- dents in this study. This finding is consistent with research con- ducted by Riska Mareta in 2018,28 which highlighted the signifi- cant relationship between PCOS and infertility. Mareta’s research concluded that individuals with PCOS face an 8.5 times greater risk of experiencing infertility. PCOS, one of the most common endocrine abnormalities among women of reproductive age, man- ifests as a collection of symptoms and signs including hyperandro- genism and anovulation resulting from disorders of the endocrine system.29,30 This condition affects approximately 5-10% of women of reproductive age, often without primary diseases in the pituitary or adrenal glands. PCOS is closely associated with chronic inflam- matory processes, with sufferers often exhibiting high levels of visceral fat due to insulin resistance mechanisms.28,31 Conclusions This study reveals several factors that significantly impact infertility, including a history of abdominal surgery, BMI, a diag- nosis of endometriosis, and PCOS. Conversely, menstrual cycle factors and menstrual pain levels were found to have no effect on infertility. It is recommended that healthcare professionals increase education about infertility within the community to enhance public awareness. Additionally, society should prioritize factors such as age at marriage, nutritional status, and lifestyle choices to mitigate the incidence of infertility. References 1. Bahar F, Zalika P, Lestari SW, et al. Male infertility as a bad news: A review. J Glob Pharma Technol 2019;11:109-14. 2. Alhassan A, Ziblim AR, Muntaka S. A survey on depression among infertile women in Ghana. BMC Womens Health 2014;14:42. 3. Novrika B. Hubungan mekanisme koping dengan tingkat kece- masan pada pasangan infertil di RSIA Annisa Jambi tahun 2015. Ris Inf Kesehat 2018;6:184. 4. Kemenkes RI, Kementrian Kesehatan Republik Indonesia. Hasil Riset Kesehatan Dasar Tahun 2018;1689-99. 5. Ngai F-W, Loke AY. Relationships between infertility-related stress, family sense of coherence and quality of life of couples with infertility. Hum Fertil 2022;25:540-7. Transforming Healthcare in Low-Resource Settings: A Multidisciplinary Approach Towards Sustainable Solutions [Healthcare in Low-resource Settings 2024;12:11985] [page 515] Non -co mmerc ial us e o nly 6. Bhattacharjee NV, Schumacher AE, Aali A, et al. Global fertil- ity in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021. Lancet 2024;403:2057-99. 7. Ferreira M, Antunes L, Duarte J, Chaves C. Influence of infer- tility and fertility adjustment on marital satisfaction. Procedia Soc Behav Sci 2015;171:96-103. 8. Fritz MA, Speroff L. Female infertility. In: Clinical Gynecologic Endocrinology and Infertility. 8th ed. Wolters Kluwer Health; 2011. 9. Santoso B, Rahmawati NY, Sa’adi A, et al. Elevated peritoneal soluble endoglin and GDF-15 in infertile women with severe endometriosis and pelvic adhesion. J Reprod Immunol 2021;146. 10. Dağ ZÖ, Dilbaz B. Impact of obesity on infertility in women. J Turkish Ger Gynecol Assoc 2015;16:111-7. 11. de Angelis C, Nardone A, Garifalos F, et al. Smoke, alcohol and drug addiction and female fertility. Reprod Biol Endocrinol 2020;18:21. 12. Sirait BI, Reviani N, Udjung GIVW. Factors affecting infertil- ity in women of reproductive age in the IVF programme. Int J Trop Dis Heal 2023;44:65-75. 13. Zhu L, Zhou B, Zhu X, et al. Association between body mass index and female infertility in the united states: data from national health and nutrition examination survey 2013-2018. Int J Gen Med 2022;15:1821-31. 14. Finelli R, Mottola F, Agarwal A. Impact of alcohol consump- tion on male fertility potential: a narrative review. Int J Environ Res Public Health 2021;19. 15. Kovac JR, Khanna A, Lipshultz LI. The effects of cigarette smoking on male fertility. Postgrad Med 2015;127:338-41. 16. Hashemi AH, Mozdarani H, Mozdarani S. The relationship between hormones level and body mass index with insertion and deletion (D/I) polymorphism of ACE gene in infertile patients with polycystic ovary syndrome. Bali Med J 2017;6:90-6. 17. Benksim A, Elkhoudri N, Addi RA, et al. Difference between primary and secondary infertility in Morocco: frequencies and associated factors. Int J Fertil Steril 2018;12:142-6. 18. Igarashi H, Takahashi T, Nagase S. Oocyte aging underlies female reproductive aging: biological mechanisms and thera- peutic strategies. Reprod Med Biol 2015;14:159-69. 19. Dewi NLPMC, Lindayani IK, Rahyani NKY, Suindri NN. Gambaran Faktor-Faktor Penyebab Infertilitas Dan Tingkat Keberhasilan Program Bayi Tabung Yang Diikuti Oleh Pasangan Usia Subur. J Ilm Kebidanan (J Midwifery) 2022;10:1-8. 20. Piyakong D, Apiratanawong S, Suasing C. Insights from lead- ers on effectively addressing overweight and obesity in the Thai community. J Ners 2023;18:117-23. 21. Handini A, Mirfat M. Hubungan Usia dan Obesitas dengan Infertilitas pada pasien di Rumah Sakit Kepresidenan RSPAD Gatot Soebroto. Maj Kesehat Pharmamedika 2018;9:33. 22. Vembu R, Devi MN, Nellepalli SR, et al. Impact of body mass index on the prevalence of metabolic syndrome among infer- tile south Indian women. Int J Infertil Fetal Med 2020;10:42- 5. 23. Wiyono T, Dwiningsih SR, Widjiati W. The impact of endometriosis on intracellular calcium levels, cyclic dependent kinase 1 (Cdk1) expression, and cyclin b expression in post- ovulation oocytes of mice model. J Reprod Infertil 2023;24:232-9. 24. Kim M-R, Chapron C, Römer T, et al. Clinical Diagnosis and Early Medical Management for Endometriosis: Consensus from Asian Expert Group. Healthcare 2022;10. 25. Hendarto H. Endometriosis Dari Aspek teori sampai penan- ganan klinis. Airlangga University Press; 2015. 26. Rahmawati NY, Ahsan F, Santoso B, et al. Role of TNF super- family members lymphotoxin-α, sCD40L, and TNF-α in endometriosis-related infertility. J Endometr Pelvic Pain Disord 2024;0. 27. Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am 2012;39:535-49. 28. Mareta R, Amran R, Larasati V. Hubungan polycystic ovary syndrome (PCOS) dengan infertilitas di praktik swasta dokter obstetri ginekologi Palembang. Maj Kedokt Sriwij 2018;50:85-91. 29. Rachmawati DA, Sa’adi A, Utomo B, Tunjungseto A. Relationship between angiopoietin-like-protein-2 levels and anti-mullerian hormone levels in polycystic ovary syndrome of reproductive age. Bali Med J 2023;12:861-5. 30. Santoso B, Rusnaidi, Widjiati. Effect of alpha lipoic acid on polycystic ovary syndrome with insulin resistance. Indian J Forensic Med Toxicol 2020;14:1015-20. 31. Calcaterra V, Verduci E, Cena H, et al. Polycystic ovary syn- drome in insulin-resistant adolescents with obesity: the role of nutrition therapy and food supplements as a strategy to protect fertility. Nutrients 2021;13. Transforming Healthcare in Low-Resource Settings: A Multidisciplinary Approach Towards Sustainable Solutions [page 516] [Healthcare in Low-resource Settings 2024;12:11985] Non -co mmerc ial us e o nly