{"paper_id":"97a56e34-7398-4be0-907d-92740a6be5d5","body_text":" Corresponding author: Ahmad Dritto Kluge Rifasky \nCopyright © 2024 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. \nComparison of pregnancy success rates i n ICSI (Intracytoplasmic Sperm Injection) \nsuccess rates in cases of male and female infertility at the Graha Amerta Fertility \nClinic, RSUD Dr. Soetomo Hospital, Surabaya, for the period 2018 – 2022: A Literature \nReview  \nAhmad Dritto Kluge Rifasky 1, *, Zakiyatul Faizah 2, Jimmy Yanuar Annas 3 and Sri Ratna Dwiningsih 2\n1 Medical Study Program, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. \n2 Department of Biology Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. \n3 Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. \nMagna Scientia Advanced Research and Reviews, 2024, 12(02), 381-387 \nPublication history: Received on 01 November 2024; revised on 16 December 2024; accepted on 18 December 2024 \nArticle DOI: https://doi.org/10.30574/msarr.2024.12.2.0214 \nAbstract \nInfertility, defined as the inability to conceive after one year of unprotected intercourse (WHO, 2012), affects 8–10% of \ncouples worldwide, equivalent to 50–80 million couples, with 2 million new cases annually (WHO, 2013). In Indonesia, \n10–15% of the 39.6 million reproductive-age couples face infertility, with primary causes including sperm issues (35%), \novulatory disorders (20%), fallopian tube blockages (20%), endometriosis (20%), and idiopathic factors (10%). The \nprevalence is rising both globally and domestically, with infertile women in the U.S. pro jected to reach 7.7 million by \n2025. Assisted reproductive technologies like IVF achieve a success rate of 40 –50%, while ICSI, a more advanced \ntechnique, offers higher success rates, particularly for cases of poor sperm quality (Wulaningsih, 2021; Aurel et al., \n2023). However, routine ICSI use without clear indications should consider associated risks and costs (ASRM, 2020). \nICSI success rates have improved from 44.6% in 2014 to 59.5% in 2023 (Palermo et al., 2014; Batha et al., 2023). Further \nresearch is needed in Indonesia to comprehensively compare ICSI success rates between male and female infertility \ncases.  \nKeywords:  Infertility; In Vitro Fertilization; ICSI; Comparison; Pregnancy success rate \n1. Introduction\nInfertility, a condition marked by the inability to conceive after one year of regular, unprotected intercourse, presents \nsignificant challenges for affected couples. Infertility is divided into two types: primary and secondary, with various \ncausal factors from the male, female, or a combination of both. In women, disorders can occur in the vagina, cervix, \nuterus, fallopian tubes, ovaries, or the ovulation process. Meanwhile, in men, problems are often related to coitus, \nejaculation, and sperm quality. Othe r factors such as age, lifestyle, and stress also contribute to infertility (Novrika, \n2015). Based on data from the Central Statistics Agency (BPS) in 2021, there are 39.6 million fertile couples in Indonesia, \nwith 10 -15% of them having difficulty having children. The main causes of infertility include sperm factors (35%), \novulation disorders (20%), fallopian tube occlusion (20%), endometriosis (20%), and idiopathic factors (10%). \nInfertility is a global health problem, including in Indonesia, although it is not life-threatening or affects physical activity. \nHowever, for many couples, infertility has a major impact on family life, economy, and psychology (Hestiantoro et al., \n2013). WHO estimates that 8-10% of couples worldwide experience infertility, equivalent to 50 -80 million couples or \naround two million new cases each year. Data from the 2013 Riskesdas showed that the prevalence of infertile couples \n\n\nMagna Scientia Advanced Research and Reviews, 2024, 12(02), 381-387 \n382 \nin Indonesia reached 15-25%. In addition, the National Survey of Family Growth (NSFG) survey in the US revealed an \nincrease in infertile women from 8.4% in 1982 to 10.2% in 1995, and is predicted to reach 7.7 million in 2025 (Chandra \net al., 2013). \nIVF (In Vitro Fertilization) is one method of treating infertility with a success rate of 40-50% (Wulaningsih, 2021). One \nof the IVF techniques, ICSI (Intracytoplasmic Sperm Injection), has shown high success with the procedure of injecting \nsperm directly into the oocyte for fertilization, especially in cases of low sperm quality (Aurel et al., 2023). Some experts \neven suggest that ICSI be used routinely to prevent fertilization failure, although the risks need to be considered \ntogether with the cost of the procedure (ASRM, 2020). A 2014 study showed that the ICSI success rate reached 44.6% \nof 35,065 cases, while a 2023 study recorded a success rate of 59.5% of 377 couples (Palermo et al., 2014; Batha et al., \n2023). However, research in Indonesia is still minimal in comparing the success rate of ICSI between male and female \nfactors, so further studies are needed to update existing data \nLiterature reviews on Comparison of ICSI Pregnancy Success Rates in Male and Female Infertility Cases, is the first to \nclearly compare these two factors and are still limited. Therefore, based on the reviewed studies on infertility, further \nexploration of the ICSI method is necessary, particularly in Indonesia. This would allow for a comparison of ICSI success \nrates between male and female infertility cases.  \n2. Review Content \n2.1. Infertility \n2.1.1. Definition of Infertility \nInfertility is the inability to conceive, affecting both humans and animals, and occurs when a couple cannot achieve \npregnancy through sexual intercourse (Soleimani et al., 2023). In humans, infertility can result from various biological \nfactors but is treatable with medical technologies. Primary infertility refers to couples unable to conceive after a year of \nunprotected intercourse, while secondary infertility applies to those who previously conceived but can no longer do so \nunder similar conditions (Vander Borght & Wyns, 2018). \n2.1.2. Infertility in Male \nThe diagnostic process for male infertility typically involves a series of evaluations, including a comprehensive medical \nhistory to assess reproductive health, semen analysis to examine sperm quality (count, motility, and morphology), \nhormonal tests to me asure reproductive hormone levels, physical examinations and ultrasound to detect anatomical \nabnormalities, ejaculatory function tests, sperm DNA integrity analysis, and testicular biopsies if necessary (Schlegel et \nal., 2021). Risk factors for male infertility are categorized into three main groups: pre -testicular, testicular, and post -\ntesticular causes. Pre -testicular factors include hypothalamic and pituitary disorders, hormonal imbalances, and \ncongenital conditions affectin g spermatogenesis. Testicular factors involve issues such as varicocele, gonadotoxin \nexposure, trauma, tumors, systemic diseases, and idiopathic conditions. Post -testicular factors include reproductive \ntract obstructions, sperm motility disorders, and coit al dysfunctions like erectile issues or abnormal sexual activity \nfrequency. Additional risks include aging, obesity, alcohol consumption, smoking, exposure to environmental toxins, \nexcessive physical activity, prolonged use of laptops or mobile devices, and high stress levels, with individual variability \nin contributing factors (Amelia & Rahmanisa, 2019; Gaziansyah & Janar Wulan, 2019). \n2.1.3. Infertility in Female \nThe diagnostic process for female infertility involves various tests and procedures to identify the underlying causes. \nThese include a comprehensive medical history, physical examination to assess reproductive anatomy, and tracking \nmenstrual cycles to eval uate ovulation. Hormonal tests are performed to measure reproductive hormones, and pelvic \nultrasound (USG) is used to examine the ovaries, uterus, and fallopian tubes for structural issues like polycystic ovary \nsyndrome (PCOS), fibroids, or other abnormalities. Hysterosalpingography (HSG) checks for blockages in the fallopian \ntubes, while laparoscopy can be used to examine and treat conditions like endometriosis. Ovulation function is also \ntested using progesterone levels or ovulation monitoring tools. Comm on risk factors for female infertility include \novulation disorders, PCOS, fallopian tube problems, uterine abnormalities, increasing age, body weight issues, stress, \nreproductive infections, and sexually transmitted diseases, all of which can disrupt hormo nal balance, ovulation, or \nreproductive tract function, making it more challenging to conceive. \n\nMagna Scientia Advanced Research and Reviews, 2024, 12(02), 381-387 \n383 \n2.1.4.  Infertility solution \nSeveral treatment options for infertility in both men and women include medical care, assisted reproductive technology \n(ART), donor sperm or egg, and reproductive surgery. Medical treatments may involve medications to regulate \nmenstrual cycles, stimulate o vulation, or balance hormones, especially for conditions like hormonal imbalances, \nendometriosis, or polycystic ovary syndrome (PCOS). ART techniques, such as in vitro fertilization (IVF) or \nintracytoplasmic sperm injection (ICSI), can help couples facing fertility issues by fertilizing eggs outside the body and \nimplanting the embryo in the uterus. Donor sperm or eggs may be considered if there are issues with sperm or egg \nproduction. In some cases, surgery may be necessary to address physical conditions such as blocked fallopian tubes or \nendometriosis. \n2.2. In Vitro Fertilization (IVF) \nThe term \"test tube baby\" is more commonly used than \"In Vitro Fertilization\" (IVF), referring to the process where an \negg and sperm meet in a laboratory dish (not in the fallopian tube). This technique is typically used for women with \ndamaged or blocked fallopian tubes that cannot be repaired. In IVF, mature eggs are manually retrieved and fertilized \noutside the body, and the resulting embryos are then implanted back into the uterus for further development. Although \n\"test tube baby\" is widely recognized, IVF is the most popular assisted reproductive method, initially developed to treat \nwomen with fallopian tube issues but now also used for various fertility problems, such as poor sperm quality, ovulation \ndisorders, endometriosis, and unexplained infertility (Aisiyah Anwar et al., 2022).  \n2.2.1. Success rates of In Vitro Fertilitation (IVF) \nThe success rate of IVF using the ICSI method is relatively high. According to a study on the \"Relationship between \nfactors causing infertility and the success rate of IVF-ICSI at RSIA Putri Bunda Denpasar in 2017,\" the success rate of the \nIVF-ICSI procedure was found to be 30.8%. The Majority of female patients undergoing the procedure were aged 35 or \nyounger, accounting for 69.2%, while the majority of male patients were aged 40 or younger, accounting for 82.1% (Ayu \net al., 2020). \n2.3. Intracytoplasmic Sperm Injection (ICSI) \n2.3.1.  Definition of Intracytoplasmic Sperm Injection (ICSI) \nICSI (Intracytoplasmic Sperm Injection) is an advanced technique used in assisted reproductive technology (ART) to \naddress infertility. It involves directly injecting a single sperm into the cytoplasm of a mature egg using a specialized \npipette. The fertilized egg is then implanted into the uterus. This method aims to improve the chances of fertilization in \ncases with sperm quality or quantity issues, and is typically recommended when there are sperm abnormalities, low \nsperm count, or previous unsuccessful fertilization attempts with conventional IVF (Setiadi et al., 2012). \n2.3.2. ICSI technique \nICSI is typically performed on couples facing fertilization issues, where the husband is unable to produce sperm suitable \nfor natural conception or IVF. The wife is given hormone induction to obtain mature eggs, which are retrieved about 36 \nhours after the  administration of hCG (Mansour et al., 1994) . Prior to the ICSI procedure, the eggs are processed to \nremove surrounding cumulus cells, and only eggs with the first polar body (PB -I) are selected. The sperm are chosen \nusing selection methods such as swim-up or side migration and then immobilized to facilitate the injection. While ICSI \nhas a high fertilization rate, fertilization failure or low fertilization rates can still occur, with total fertilization fai lure \nreported at 1.29% and 3% according to (Liu et al., 1995). Selecting normal sperm for manipulation is a challenge, but \nstudies have shown that even immotile or dead sperm can still support the formation of male and female pronuclei after \nbeing injected into the egg (Saili & Said, 2005). \n2.3.3. Advantages of ICSI \nICSI is an effective solution for male infertility issues such as low sperm count, poor motility, abnormal morphology, or \nother problems, as it involves directly injecting a selected sperm into the egg, bypassing natural fertilization barriers \n(Eftekhar al., 2012). This technique increases the chances of successful fertilization by minimizing the risks associated \nwith abnormal sperm or sperm adhesion to the egg (Zheng et al., 2019). It also ensures better sperm selection, as only \nthe healthiest sperm is chosen for each egg, improving the chances of a healthy embryo development. ICSI is also \nbeneficial for women facing fertility issues like ovulation disorders or endometriosis, as it  guarantees fertilization by \ndirectly introducing sperm to the egg (Eftekhar et al., 2012). Furthermore, ICSI supports genetic selection techniques, \nsuch as embryo screening or genetic disease detection, which can help couples with genetic conditions or high -risk \nhistories avoid passing on undesirable genetic traits to their offspring (Zheng et al., 2019). \n\nMagna Scientia Advanced Research and Reviews, 2024, 12(02), 381-387 \n384 \n2.3.4. Disadvantages of ICSI \nICSI carries certain disadvantages, including higher costs compared to traditional IVF due to the complex \nmicromanipulation techniques and specialized equipment required for sperm injection into the egg (Sermondade et al., \n2013). Additionally, there is a risk of egg injury during the process, as the microneedle used to inject the sperm can \ndamage the egg, potentially affecting its ability to divide and develop properly (Wen et al., 2004). The direct selection \nof sperm by embryologists also raises concerns about undetected genetic abnormalities, which could lead to the transfer \nof embryos with genetic defects, increasing the risk of genetic disorders in the offspring (Li et al., 2006). Fur thermore, \nsome studies suggest that ICSI may be linked to a higher risk of reproductive disorders in children, although the risk \nremains low, highlighting the importance of consulting a fertility specialist before undergoing the procedure \n(Sermondade et al., 2013). \n2.3.5. Success rate of ICSI \nIt is important to note that the success rate of IVF-ICSI varies, as the outcome of the procedure does not always remain \nthe same for every cycle and depends on individual factors. In 2014, a study on ICSI showed that out of 35,065 extreme \ninfertility case s, there were 15,646 cases (44.6%) of successful ICSI with positive βhCG indications (Palermo et al., \n2014). However, in Indonesia, the success rate of IVF-ICSI in 23 IVF centers reached only 13.88%, according to available \ndata (Ayu et al., 2020). A study conducted in 2023 on 377 couples found a success rate of 59.5% for ICSI. This research \ndemonstrated the success rate of ICSI in patients with infertility issues in both men and women (Batha et al., 2023). \n2.3.6. Factors influencing the success of ICSI \nSeveral factors can influence the success of Intracytoplasmic Sperm Injection (ICSI). First, the quality and quantity of \nsperm play a crucial role, with sperm that has good motility, normal morphology, and sufficient quantity increasing the \nchances of succ essful conception (Nadila & Pambudi, 2023).  The quality of the oocytes is also important, as mature \noocytes with a healthy nucleus are more likely to be successfully fertilized . Additionally, the skill and experience of the \nembryologist performing ICSI are critical in ensuring proper sperm injection and maximizing fertilization success. The \nage of the woman can affect ICSI success, as older women generally have lower quality oocy tes, which can negatively \nimpact outcomes . Overall health conditions, such as endometriosis, polycystic ovary syndrome (PCOS), or hormonal \nimbalances in women, and genetic or sperm abnormalities in men, can also affect ICSI success. Finally, the quality of the \nembryo post-fertilization is crucial for successful implantation and the potential for a successful pregnancy (Nadila & \nPambudi, 2023). \n3. Conclusion \nThis study confirms that ICSI success rates are higher in male infertility cases compared to female cases. Biological \nfactors, age, and gender significantly impact the success of ICSI procedures. These findings support ICSI as the preferred \nmethod for addressing male infertility and underscore the need for tailored strategies to improve ICSI outcomes in \nfemale infertility. These findings highlight the importance of gender-specific treatment approaches. For men, the focus \nshould be on evaluating sperm quality and optimizing ICSI techniques. For women, improving ovarian health and \naddressing reproductive conditions should be prioritized. \nFurther research is needed to explore additional factors influencing ICSI success, such as genetic, hormonal, and \nenvironmental factors in Indonesia. \nCompliance with ethical standards \nAcknowledgments \nAll praise and gratitude we offer to Allah SWT for His grace and blessings so that this research can be completed \nproperly. This research would not have been possible without the support and contribution of various parties who have \nhelped during the process of compiling and completing this journal. \nWe express our deepest appreciation to: \n• RSUD Dr. Soetomo Surabaya, especially the Graha Amerta Fertility Clinic, for the permission and data access \nprovided, as well as support during this research process. \n• Supervisors, Dr. Zakiyatul Faizah, dr., M.Kes., and Dr. Jimmy Yanuar Annas, Sp.OG (K), for their invaluable \nguidance, input, and direction in compiling and completing this research. \n\nMagna Scientia Advanced Research and Reviews, 2024, 12(02), 381-387 \n385 \n• Family, especially parents, who always provide moral support, prayers, and motivation without stopping \nduring the research process. \n• Fellow students at the Faculty of Medicine, Airlangga University who have helped in discussions, shared ideas, \nand provided encouragement in completing this research. \n• All parties who have directly or indirectly helped in data collection, analysis, and preparation of this journal. \nWe hope that this research can provide benefits for the development of medical science, especially in the field of assisted \nreproductive technology, and become a reference for further research. \nDisclosure of conflict of interest \nNo conflict of interest to be disclosed.  \nReferences \n[1] Agarwal, A., Mulgund, A., Hamada, A. and Chyatte, M.R. 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