{"paper_id":"5899e3f5-0fec-4093-88aa-a4b61efce562","body_text":"~ 28 ~ \nInternational Journal of Clinical Obstetrics and Gynaecology 2025; 9(3): 28-34 \n \nISSN (P): 2522-6614 \nISSN (E): 2522-6622 \n© Gynaecology Journal \nwww.gynaecologyjournal.com \n2025; 9(3): 28-34 \nReceived: 25-02-2025 \nAccepted: 29-03-2025 \n \nDr. Roya Rozati \nProfessor and H.O.D, Department \nof Obst & Gynec, Shadan Institute \nof Medical Sciences, Medical and \nResearch Director, Medical Health \nand Research Institute (MHRI), \nHyderabad, Telangana, India \n \nMuhammad Siddique Ahmed Khan \nProfessor H.O.D, Department of \nBiochemistry, Shadan Institute of \nMedical Sciences, Hyderabad, \nTelangana, India \n \nWajeeda Tabasum \nM.Sc. Genetics, Osmania \nUniversity, Research Scholar, \nMedical Health and Research \nInstitute (MHRI),  \nHyderabad, Telangana, India \n \nAyapati Gautam Mehdi  \nScientist C, Medical Health and \nResearch Institute (MHRI), \nHyderabad, Telangana, India \n \nVikram Aiman Ayapati \nScientist C, Medical Health and \nResearch Institute (MHRI), \nHyderabad, Telangana, India \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nCorresponding Author: \nDr. Roya Rozati \nProfessor and H.O.D, Department \nof Obst & Gynec, Shadan Institute \nof Medical Sciences, Medical and \nResearch Director, Medical Health \nand Research Institute (MHRI), \nHyderabad, Telangana, India \n \nTo evaluate the effectiveness of GnRH agonist and \ncombined oral contraceptives protocols in \nIntracytoplasmic Sperm Injection (ICSI) cycles for \npatients with different stages of endometriosis \n \nRoya Rozati, Muhammad Siddique Ahmed Khan, Wajeeda Tabasum, \nAyapati Gautam Mehdi and Vikram Aiman Ayapati \n \nDOI: https://www.doi.org/10.33545/gynae.2025.v9.i3a.1623  \n \nAbstract \nBackground: Endometriosis, a chronic gynecological condition affecting reproductiv e-age women, is \nstrongly associated with infertility. Gonadotropin -releasing hormone agonists (GnRH -a) are widely used \nfor endometriosis management and may improve outcomes in assisted reproductive technology (ART). \nThis study to assess the reproductive ou tcomes of endometriosis patients undergoing controlled ovarian \nstimulation and ICSI cycles with two treatment regimens: GnRH agonists and combined oral \ncontraceptives (COCs). \nMethods: It is a prospective study conducted from March 2020 to March 2024. A total of 100 patients with \nstage I–IV endometriosis were randomly assigned to two treatment groups: a GnRH agonist group ( N=50) \nand a combined oral contraceptive (COC) group ( N=50). Clinical, hormonal, and reproductive parameters \nwere assessed and compared between the groups. \nResults: The GnRH agonist group demonstrated superior reproductive outcomes compared to the COC’s \ngroup, with higher clinical pregnancy rates (76% vs. 72%), ongoing pregnancy rates (68% vs. 56%), and \ncumulative live birth rate per patient  (50% vs. 46% for stage I –II and 40% vs. 38% for stage III –IV). \nAlthough the GnRH agonist group required higher gonadotropin doses, they exhibited improved embryo \nquality and implantation success. Additionally, miscarriage rates were lower in the GnRH agon ist group \n(6% vs. 12%) compared to COC’s group  \nConclusion: Both regimens were effective in enhancing reproductive outcomes, however, the GnRH \nagonist protocol was associated with higher clinical pregnancy and live birth rates, particularly in patients \nwith advanced-stage endometriosis. The administration of GnRH agonists in patients with varying stages of \nendometriosis may enhance ICSI outcomes compared to the COC protocol. Optimizing treatment strategies \nis essential to improving reproductive outcomes in endometriosis-associated infertility. These findings \nhighlight the importance of tailored treatment protocols to enhance reproductive success in endometriosis \npatients undergoing ART. \n \nKeywords: Endometriosis, GnRH agonists, ICSI, ART, enhancing reproductive, endometriosis patients \n \nIntroduction  \nEndometriosis is a common gynecological disorder characterized by the growth of tissue similar \nto the endometrium outside of the uterus [1]. It affects 6% to 11% of women of reproductive age, \noften leading to symptoms such as dyspareunia, dysmenorrhea and infertility, and is observed in \nup to 50% of women experiencing infertility [2]. The primary symptoms of endometriosis include \nchronic pelvic pain, dysmenorrhea, dyspareunia, and infertility [3]. It is a multifacto rial disease \nthat directly impairs fertility by disrupting the normal anatomy of the fallopian tubes and \novaries. Indirectly, it contributes to infertility through inflammatory responses and oxidative \nstress, which can compromise oocyte quality [4]. \nLaparoscopy is a gold standard method to be performed to obtain a definitive diagnosis of \nendometriosis based on pathology seen and obtained at the time of surgery [5]. The \nadministration of a GnRH agonist in the postoperative setting aims to eradicate microscop ic \nendometriotic lesions that may not be visualized or resected during surgery, while also inhibiting \nthe development of new lesions [6]. Patients with suspected early -stage endometriosis are \ninitially managed with medical therapy, including oral contracep tives and nonsteroidal anti -\ninflammatory drugs (NSAIDs) [7]. \n\n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 29 ~ \nFor cases where pain persists despite first -line treatment, \ngonadotropin-releasing hormone (GnRH) analogues are \nconsidered a second-line therapeutic option [8]. \nGonadotropin-releasing hormone a gonists (GnRHa) are widely \nused in the management of endometriosis. These synthetic \nanalogs of gonadorelin, a hypothalamic hormone, initially \nstimulate the pituitary gland to release luteinizing hormone (LH) \nand follicle-stimulating hormone (FSH), which re gulate ovarian \nproduction of estrogen and progesterone, key hormones in the \nmenstrual cycle [9]. GnRH -a competitively binds to GnRH \nreceptors in the pituitary gland, inhibiting the release of \nendogenous GnRH. This suppression results in decreased \novarian h ormone secretion, effectively inducing pituitary down \nregulation [10]. Additionally, GnRH -a, prevents premature \nluteinization of follicles, enhancing follicular synchronization \nand development. It also mitigates inflammatory responses, \noptimizes the pelvic microenvironment, and improves oocyte \nand embryo quality [11]. \nGnRH-a can effectively prevent premature luteinization of \nfollicles, promoting better synchronization of follicular growth \nand development.  \n \nGnRH Agonist Long Protocol (Depot) \nAll 50 women wil l receive three Zoladex 3.65 mg injections \nsubcutaneously (SC). The injections are given either as a single \ndose or divided into two doses, 6 weeks apart. After the Zoladex \ninjections, controlled ovarian stimulation (COS) will be \ninitiated. All patients were informed of the potential side effects \nassociated with GnRH -a therapy, including hot flushes, \ndepression, vaginal dryness, and mild but reversible bone loss. \nGnRH-a, was administered monthly for a total of five or six \ncycles. The dosage of FSH will be i ndividually determined for \neach woman. GnRH antagonist will be given if needed during \nthe ovarian stimulation phase. Ovum pickup will be performed. \nFour months after the protocol initiation, women are scheduled \nfor an appointment at the IVF department. Women are scheduled \nfor an appointment precisely 28 days after the last Zoladex \ninjection for further assessment. Full suppression will be done \nduring this appointment. Ovarian stimulation is commenced with \nsubcutaneously injected gonadotropins (FSH). The pro tocol \nconcludes with Frozen Embryo Transfer (FET).  \n \nCombined Oral Contraceptives \nIn the Combined Oral Contraceptives (COC) group, all 50 \nwomen will undergo a three -month treatment with continuous \nCOC therapy, typically with ethinyl estradiol/levonorgestre l \n30/150μg, or other one -phase sub -50 OCs if previously used. \nAfter completing the COC regimen, women are instructed to \ncontact the IVF department on the first day of withdrawal \nbleeding. On the second day of bleeding, they will visit the IVF \ncenter to ini tiate suppression of the luteinizing hormone (LH) \npeak. Ovarian stimulation with subcutaneous gonadotropins \n(FSH) will begin one day later, with dosage individualized for \neach patient. Outcomes of IVF/ICSI cycles with COH protocols \nincluding GnRH agonists and COC were analyzed among the \nstudy groups. \n \nMethodology \nIt is a prospective study which was conducted between March \n2020 and March 2024 and included 100 infertile women \ndiagnosed with different stages of endometriosis confirmed by \nlaparoscopy and divide d into two groups. First group GnRH \nagonist ( N=50) and COC’S ( N=50). All participants were \nundergoing intracytoplasmic sperm injection (ICSI) cycle at \nMHRT Hospital and Research Center, Hyderabad, Telangana, \nIndia. The study was approved by the Institution al Ethics \nCommittee. Informed consent was obtained from all \nparticipants, permitting the collection and analysis of their \nclinical and laboratory data, including medical history, for the \npurpose of clinical. \n \nThe study included patients who met the followi ng inclusion \ncriteria \n Women under the age of 40 with a confirmed diagnosis of \nendometriosis, either through laparoscopic evaluation and \nsurgical resection performed at least one year prior to study \nenrollment or the presence of ovarian endometriotic cysts \nidentified via ultrasound at the start of the study \n A body mass index (BMI) of less than 28 kg/m² \n A diagnosis of infertility with an indication for in vitro \nfertilization (IVF) or intracytoplasmic sperm injection \n(ICSI). \n \nEndometriosis was classified based  on the ASRM guidelines, all \npatients were followed up through the completion of surgical \nprocedures, postoperative GnRH -a therapy, up to three ART \ncycles, and a four-week follow-up period.  \n \nStatistical Analysis \nA comparative analysis was conducted betwee n the two groups \nreceiving different stimulation protocols. Continuous variables \nwere analyzed using one -way ANOVA, while categorical \nvariables were assessed with the Chi -square test. Pre-stimulation \ncycle characteristics were evaluated using the Kruskal -Wallis H-\ntest for continuous variables and Pearson's Chi-square or Fisher's \nexact test for categorical variables. All statistical tests were two -\ntailed, with a significance level set at p<0.05. A 95% confidence \ninterval was used, and all statistical analyse s were performed \nusing SPSS version 23.0. \n \nAssisted Reproductive Technologies \nIn patients who underwent surgery, ovarian stimulation \ncommenced following down -regulation with 0.1 mg of GnRH -a \nusing the long protocol. Daily subcutaneous injections of GnRH -\na (Decapeptyl 0.1; Ferring, Kiel, Germany) were initiated on \ncycle day 18. Beginning on day 3 of the subsequent cycle, \nrecombinant FSH (Gonal -F; Serono) was administered daily at \ndoses ranging from 150 IU to 300 IU. Ovulation was triggered \nwith 10,000 IU of hCG (Pregnesin; Serono), and \nultrasonography-guided follicular puncture was performed 35 to \n36 hours post-trigger. \nIn patients who received GnRH -a treatment, ovarian stimulation \ncommenced exactly two weeks after the final depot injection of \nGnRH-a, with daily subcutaneous administration of recombinant \nFSH (Gonal-F; Serono) at doses ranging from 150 IU to 300 IU. \nThe subsequent treatment protocol, including ovulation \ninduction, follicular puncture, and luteal phase support, followed \nthe same procedure as des cribed previously. A maximum of \nthree IVF/ICSI cycles were included in the analysis. \n \nAssessment of Pregnancy \nFourteen days after Embryo Transfer (ET), pregnancy was \nassessed through a β -hCG assay and endometrial thickness \nmeasurement. Only clinical pregnancies were recorded, defined \nby rising β-hCG levels and confirmed ultrasonography detection \nof an amniotic sac. \n \nResults \nA total of 100 eligible p atients were enrolled and included in the \nstudy. Patients were randomized into two groups patients with \n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 30 ~ \nstage I–II endometriosis-GnRH agonist (N= 16), COCs (N= 21) \nand stage III -IV endometriosis GnRH agonist (N= 34), COCs \n(N= 29). The Figure 1 of this stud y evaluated 100 endometriosis \npatients, comparing two treatment protocols. Group 1 (GnRH \nagonist long protocol, N=50) included 19 fresh embryo transfers \n(ET) and 31 frozen -thawed ET, resulting in 5 biochemical \npregnancies, 38 clinical pregnancies, 34 ongoi ng pregnancies, \nand 32 live births -20 in patients with minimal to mild \nendometriosis and 12 in those with moderate to severe \nendometriosis. Group 2 (combined oral contraceptives, N=50) \nhad 16 fresh ET and 34 frozen -thawed ET, yielding 4 \nbiochemical pregnan cies, 31 clinical pregnancies, 28 ongoing \npregnancies, and 16 live births -11 in minimal to mild \nendometriosis and 5 in moderate to severe cases. These findings \ndemonstrate the efficacy of both regimens in enhancing \nreproductive outcomes, with success varyi ng according to \nendometriosis severity. \nThe Table 1 in this study illustrates the socio -demographic and \nclinical profiles of endometriosis patients treated with GnRH \nagonists (N=50) and Combined Oral Contraceptives (N=50) \nwere compared. The GnRH agonist gr oup had a mean age of \n32.22±4.42 years, BMI of 23.3±2.9 kg/m², and lower AMH \n(0.91±1.1 ng/ml) and AFC (4 [3–4]). A higher proportion of \npatients in this group had ASRM stage III-IV (68%) and primary \ninfertility (29). In contrast, the Combined Oral Contrace ptives \ngroup had an average age of 33.41±3.42 years, lower BMI \n(22.42±2.78 kg/m²), and higher AMH (2.52±3.8 ng/ml) and \nAFC (5 [6–8]). This group had a higher incidence of secondary \ninfertility (36%) and more patients with ASRM stage I -II (42%). \nBoth groups  had similar infertility durations, but the GnRH \nagonist group had more previous failed cycles and a higher \nproportion of nulliparous patients. \nIn the Table 2 shows the comparative study of Controlled \nOvarian Stimulation (COS) and intracytoplasmic sperm injection \n(ICSI) cycles in endometriosis patients using a GnRH agonist \nprotocol versus a combined oral contraceptive (COC) protocol, \nseveral key outcomes were assessed. The total dose of \ngonadotropins was significantly higher in the GnRH agonist \ngroup (2700. 0 IU [2250.0 -3440.6 IU]) compared to the COC \ngroup (2400.0 IU [1846.9 -3075.0 IU]). Both groups received \nsimilar doses of LH (GnRH agonist: 1093.3±458 IU, COC: \n1089.5±314.6 IU), while the total FSH dose was markedly \nhigher in the COC protocol group (3612±22 72.8 IU) compared \nto the GnRH agonist group (595.13±2158.7 IU).  \nThe duration of gonadotropin stimulation was similar in both \ngroups, with an average of 11±2 days. Endometrial thickness on \nthe trigger day was significantly thinner in the GnRH agonist \ngroup (3.58±1.73 mm) compared to the COC group (5.53±3.42 \nmm). Serum estradiol levels on the hCG trigger day were \nsignificantly lower in the GnRH agonist group (1832.2±889.6 \npg/mL) compared to the COC group (2200.9±806.9 pg/mL).  \nIn terms of oocyte retrieval, t he GnRH agonist group yielded a \nhigher number of oocytes per patient (5 [3 -6] vs. 4 [3-5]), with a \nhigher number of mature oocytes (MII) retrieved (4 [3-5] vs. 3 [3-\n5]) in comparison to COC group. The number of immature \noocytes (MI + PI) retrieved was simi lar in both groups (GnRH \nagonist: 2 -3 [1 -3], COC:2) [1-3]. Fertilization rates were \ncomparable between the groups, with the GnRH agonist group \nfertilizing 4 oocytes (2 -4) per patient and the COC group \nfertilizing 3 oocytes (2 -3). Both protocols produced si milar \nnumbers of blastocysts, with the GnRH agonist group generating \n1 (1 -2) blastocyst per patient and the COC group generating 1 \n(0-1) blastocyst per patient. These findings indicate that while \ndifferences exist in gonadotropin dosing and ovarian respons e \nbetween the two protocols, fertilization and blastocyst formation \nrates were similar in both groups. \nIn this study, reproductive outcomes were evaluated in 100 \nEndometriosis patients (N=50 per group) treated with either \nGnRH agonist or Combined Oral Cont raceptives (COC) \nprotocols. For fresh single embryo transfer (SET), the success \nrate for patients with Stage I -II endometriosis was 12% (6/50) in \nthe GnRH agonist group and 14% (7/50) in the COC group. For \nStage III-IV endometriosis, the success rates were  6% (3/50) for \nGnRH agonists and 8% (4/50) for COC. In frozen single embryo \ntransfer (FET), success rates in Stage I -II endometriosis were \n48% (24/50) for GnRH agonist and 52% (26/50) for COC, while \nfor Stage III -IV endometriosis, the success rates were 34 % \n(17/50) for GnRH agonist and 26% (13/50) for COC. The \nbiochemical pregnancy rates were similar between the two \ngroups, with 10% (5/50) in the GnRH agonist group and 8% \n(4/50) in the COC group. The clinical pregnancy rate (CPR) was \n76% (38/50) in the GnRH  agonist group and 72% (36/50) in the \nCOC group, while ongoing pregnancy rates were 68% (34/50) \nand 56% (28/50), respectively. The miscarriage rate per \npregnancy was lower in the GnRH agonist group (6%) compared \nto the COC group (12%). CPR per started cycl e was 46% \n(23/50) for GnRH agonist and 34% (17/50) for COC. \nCumulative CPR per patient was 38% (19/50) for GnRH agonist \nand 40% (20/50) for COC. The cumulative live birth rates per \npatient were comparable between the two groups, with 50% \n(25/50) for Stage I-II endometriosis and 40% (20/50) for Stage \nIII-IV endometriosis in the GnRH agonist group, and 46% \n(23/50) and 38% (19/50), respectively, in the COC group. \nStatistical analysis  \nIn the Table 3, Depicts Reproductive outcomes in endometriosis \npatients treated with GnRH agonists (N=50) or Combined Oral \nContraceptives (N=50) protocols were evaluated. In fresh single \nembryo transfer (SET) cycles, the success rate for patients with \nStage I -II endometriosis was 12% (6/50) in the GnRH agonist \ngroup and 14% (7/50)  in the COC group. For Stage III -IV \nendometriosis, the success rates were 6% (3/50) for GnRH \nagonists and 8% (4/50) for COC (Figure 2).  \nFor frozen SET, success rates in Stage I -II endometriosis were \n48% (24/50) for GnRH agonist and 52% (26/50) for COC, wh ile \nfor Stage III -IV endometriosis, the success rates were 34% \n(17/50) for GnRH agonist and 26% (13/50) for COC (Figure 3).  \nThe biochemical pregnancy rates were similar between the two \ngroups, with 10% (5/50) in the GnRH agonist group and 8% \n(4/50) in the COC group. The clinical pregnancy rate (CPR) was \n76% (38/50) in the GnRH agonist group and 72% (36/50) in the \nCOC group, while ongoing pregnancy rates were 68% (34/50) \nand 56% (28/50), respectively.  \nThe miscarriage rate per pregnancy was lower in the GnR H \nagonist group (6%) compared to the COC group (12%). CPR per \nstarted cycle was 46% (23/50) for GnRH agonist and 34% \n(17/50) for COC. Cumulative CPR per patient was 38% (19/50) \nfor GnRH agonist and 40% (20/50) for COC.  \nThe cumulative clinical pregnancy ra te per patient was 62% for \nthe GnRH agonist group, versus 54% for the Combined Oral \nContraceptives group. Furthermore, the cumulative live birth \nrate was significantly higher in the GnRH agonist group, with \n50% in Stage I -II and 40% in Stage III -IV, compar ed to 46% \nand 38%, respectively, in the Combined Oral Contraceptives \ngroup (Figure 4). These findings underscore the superior \nreproductive outcomes associated with GnRH agonist treatment \nin endometriosis patients. \n \nDiscussion \nThis study evaluated the reproductive outcomes of two treatment \nregimens-GnRH agonists and Combined Oral Contraceptives \n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 31 ~ \n(COCs) in patients with endometriosis. The GnRH agonist group \nexhibited lower AMH and AFC levels, reflecting a diminished \novarian reserve, which aligns with the ovari an suppression \ncommonly seen in both endometriosis sand GnRH agonist \ntreatment. The reduction in AMH levels indicates a loss of \nfollicular reserve, particularly in women with advanced \nendometriosis (Stage III -IV), where ovarian damage is \nfrequently observe d. The COCs group demonstrated higher \nAMH and AFC levels, indicating a better ovarian reserve and \nless ovarian dysfunction. Elevated AMH is correlated with \nenhanced fertility potential which may explain the higher \nprevalence of secondary infertility (36%) and Stage I -II \nendometriosis (42%) in this group -conditions generally \nassociated with more favorable fertility outcomes. \nSecondary infertility in these women is more likely attributed to \nfactors such as fallopian tube function or luteal phase \nabnormalities, rather than ovarian dysfunction [12]. The greater \nproportion of Stage I-II patients in the COCs group suggests that \ninfertility may primarily result from other factors, including \npelvic adhesions or alterations in the endometrial environment. \nNulliparous women with endometriosis often experience more \nsevere infertility due to the prolonged effects of the disease, such \nas pelvic adhesions and compromised oocyte quality [13]. The \ngreater number of previous failed cycles in the GnRH agonist \ngroup suggests mo re severe or resistant infertility, which likely \ncontributed to less favorable ART outcomes. While GnRH \nagonist therapy can enhance fertility by reducing inflammation \nand creating a more favorable hormonal environment [14], the \nseverity of the disease and the presence of prior failed cycles \nmay still limit reproductive success. \nThe GnRH agonist group required higher doses of gonadotropins \n(2700.0 IU vs. 2400.0 IU) and FSH (595.13±2158.7 IU vs. \n3612±2272.8 IU) compared to the COCs group. Despite these \ndifferences, the stimulation durations were similar between both \ngroups (11±2 days), suggesting that GnRH agonist therapy \nrequired a more intensive stimulation protocol to achieve a \ncomparable ovarian response. \nThe COCs group demonstrated significantly thicker e ndometrial \nlinings (5.53±3.42 mm vs. 3.58±1.73 mm) and higher serum \nestradiol levels on the hCG trigger day (2200.9±806.9 pg/mL vs. \n1832.2±889.6 pg/mL), which corresponds with the established \nrole of COCs in promoting endometrial receptivity by \nmaintaining stable hormonal levels [12]. In contrast, GnRH \nagonists induce a hypo -estrogenic state, leading to thinner \nendometrial linings, which may compromise implantation \nsuccess [14].  \nThe GnRH agonist group retrieved slightly more oocytes (4 vs. \n3), with compara ble numbers of mature oocytes (MII) in both \ngroups. The GnRH group had a higher incidence of immature \noocytes (2 -3 vs. 2), likely due to COCs' suppressive effect on \novarian function [13]. Additionally, the GnRH agonist group had \nmore fertilized oocytes (4 vs. 3), suggesting better fertilization \noutcomes despite a thinner endometrial lining. Both groups \nproduced a similar number of embryos (3), indicating \ncomparable effectiveness in embryo production despite \ndifferences in ovarian stimulation and endometrial response. \nIn fresh single embryo transfer (SET) cycles, the success rate for \npatients with Stage I -II endometriosis was 12% (6/50) in the \nGnRH agonist group and 14% (7/50) in the COC group. For \nStage III-IV endometriosis, the success rates were 6% (3/50) for \nGnRH agonist and 8% (4/50) for COC [14] \nFor frozen SET, success rates in Stage I -II endometriosis were \n48% (24/50) for GnRH agonist and 52% (26/50) for COC, while \nfor Stage III -IV endometriosis, the success rates were 34% \n(17/50) for GnRH agonist and 2 6% (13/50) for COC. These \nfindings align with previous research suggesting that GnRH \nagonists may optimize the ovarian environment, improving \nembryo implantation and mitigating the impact of endometriosis \non fertility [15]. Additionally, the GnRH agonist g roup had lower \nmiscarriage rates (6%) compared to the COCs group (12%), \nhighlighting the treatment's role in enhancing reproductive \noutcomes. \nThe cumulative clinical pregnancy rate per patient was \nsignificantly higher in the GnRH agonist group (38%) compar ed \nto the COCs group (40%), with notably higher live birth rates in \nStage I-II (50% vs. 46%) and Stage III -IV (40% vs. 38%) for the \nGnRH agonist group in comparison to the COC’s group. These \nresults further support the evidence that GnRH agonist therapy \nnot only enhances short -term pregnancy outcomes but also \npromotes long -term fertility success in women with \nendometriosis [12]. \nThe improved outcomes in the GnRH agonist group, especially \nin advanced stages of endometriosis, highlight the potential of \nGnRH agonists to alleviate the effects of severe disease, such as \npelvic adhesions and ovarian dysfunction, which can negatively \naffect fertility [15]. These findings align with previous \nprospective studies showing the beneficial impact of GnRH \nagonists on fertility in patients with endometriosis [13]. \n \nTable 1: Socio-demographic characteristics and clinical profiles from Endometriosis patients with GnRH agonist and combined oral contraceptives protocol \n \nClinical characteristics GnRH agonist (N=50) Combined Oral Contraceptives Protocol (N=50) P-Value \nPatient age (years) 32.22±4.42 33.41±3.42 0.13 \nBMI (kg/m2) 23.3 ± 2.9 22.42± 2.78 0.12 \nAMH (ng/ml) 0.91±1.1 2.52±3.8 0.004 \nSubfertility \nPrimary Infertility \nSecondary Infertility \n \n29(58%) \n21(42%) \n \n36(72%) \n14(28%) \n \n0.20 \n \nBaseline AMH 1.19 (1– 1.26) 1.52(1– 1.49)  \nAFC 4(3-4) 5 (6-8) 1.00 \nBasal FSH (IU/L) 8.01 ± 1.91 7.21 ±1.92 0.03 \nDuration of infertility (years) 2.82 ±1.6 2.5 ±1.2 0.26 \nASRM stage I-II 16(32%) 21(42%) 0.40 ASRM stage III-IV 34(68%) 29(58%) \nPrevious failed Cycles \n0 \n \n13(26%) \n \n22(44%)  \n \n0.26 1 20(40%) 16(32%) \n>2 17(34%) 12(24%) \nParity    \n0 26(52%) 18(36%) 0.15 1 24(48%) 32(64%) \n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 32 ~ \nTable 2: Controlled ovarian stimulation and ICSI cycles in Endometriosis patients with GnRH agonist and combined oral contraceptives protocol \n \nVariable GnRH agonist (N=50) Combined Oral Contraceptives Protocol (N=50) P-Value \nTotal dose of gonadotropins 2700.0 (2250.0-3440.6) 2400.0 (1846.9-3075.0) 0.001 \nTotal dosage of FSH (IU) 595.13±2158.7 3612±2272.8 0.001 \nTotal dosage of LH (IU) 1093.3±458 1089.5±314.6 0.91 \nDuration of Gonadotrophin stimulation (days) 11±2 11±2 1.00 \nEndometrial thickness(mm) 3.58± 1.73 5.53 ±3.42 0.0005 \nSerum estradiol levels on hCG trigger day (pg/mL) 1832.2 ±889.6(1826.6-2097.7) 2200.9±806.9(2072.5-2430.5) 0.03 \nTotal number of oocytes retrieved per patient 5(3-6) 4(3-5) 1.00 \nNo of Mature Oocytes retrieved (MII) per patient 4(3-5) 3(3-5) 1.00 \nNo of Immature oocytes (MI+PI) per patient 2-3(1-3) 2(1-3) 0380 \nNo. of oocytes fertilized per patient 4(2-4) 3(2-3) 1.00 \nTotal number of Blastocysts per patient 1(1-2) 1(0-1) 0.51 \n \nTable 3: Reproductive outcomes of cycles in endometriosis patient groups and combined oral contraceptives protocol \n \nVariable GnRH agonist (N=50) Combined Oral Contraceptives Protocol (N=50) P-Value \nFresh Single Embryo Transfer    \nStage I-II 6/50(12%) 7/50(14%) 1.00 \nStage III-IV 3/50(6%) 4/50(8%) 1.00 \nFrozen Single Embryo Transfer    \nStage I-II 24/50(48%) 26/50(52%) 0.81 \nStage III-IV 17/50(34%) 13/50(26%) 0.51 \nBiochemical pregnancy 5/50(10%) 4/50(8%) 1.00 \nClinical Pregnancy Rate (CPR) 38/50(76%) 36/50(72%) 0.81 \nOngoing Pregnancy 34/50(68%) 28/50(56%) 0.30 \nMiscarriage Rate per Pregnancy 3/50 (6%) 6/50 (12%) 0.48 \nCPR per Started Cycle 23/50 (46%) 17/50 (34%) 0.30 \nCumulative CPR per Patient 19/50 (38%) 20/50 (40%) 1.00 \nCumulative Live Birth Rate per patient    \nStage I-II 25/50(50%) 23/50(46%) 0.84 \nStage III-IV 20/50(40%) 19/50(38%) 1.00 \n \n \n \nFig 1: Details of the flowchart illustrating participant progression and outlining the primary reproductive outcomes of the enrolled patients. \nGnRHa, gonadotropin-releasing hormone agonist, combined oral contraceptives \n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 33 ~ \n \n \nFig 2: Illustrates the fresh single embryo transfer (SET) process in Stage I-II and Stage III-IV, comparing the use of GnRH agonists and  \ncombined oral contraceptives (COCs) \n \n \n \nFig 3: Illustrates the Frozen single embryo transfer (SET) process in Stage I-II and Stage III-IV, comparing the use of GnRH agonist and  \ncombined oral contraceptives (COCs). \n \nConclusion \nThis study highlights the effectiveness of both GnRH agonist \nand Combined Oral Contraceptive (COC) protocols in managing \nendometriosis-related infertility. While GnRH agonists resulted \nin higher oocyte yield and clinical pregnancy rates in moderat e \nto severe endometriosis, COC protocols showed comparable \noutcomes in minimal to mild cases with fewer side effects and \nlower gonadotropin requirements. Frozen Embryo Transfer \n(FET) outcomes were generally superior across both groups. \nThese findings under score the importance of individualized \ntreatment strategies based on endometriosis stage and patient \nprofile to optimize assisted reproductive outcomes, offering \nvaluable insights for clinicians in tailoring fertility treatment \nplans. \n \nDisclosure Statement \nAuthors have no competing interests to declare. \n \nAcknowledgments \nWe acknowledge all the authors of the manuscript \nConflict of Interest \nNot available  \n \nFinancial Support \nNot available \n \nReferences  \n1. Smolarz B, Szyłło K, Romanowicz H. Endometriosis: \nepidemiology, classification, pathogenesis, treatment and \ngenetics (review of literature). 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To evaluate \nthe effectiveness of GnRH agonist  and combined oral contraceptives \nprotocols in Intracytoplasmic Sperm Injection (ICSI) cycles for patients \nwith different stages of endometriosis . International Journal of Clinical \nObstetrics and Gynaecology. 2025;9(3):28-34.  \n \n \nCreative Commons (CC) License \nThis is an open -access journal, and articles are distributed under the terms \nof the Creative Commons Attribution -Non Commercial-Share Alike 4.0 \nInternational (CC BY -NC-SA 4.0) License, which allows others to remix, \ntweak, and build upon the work non -commercially, as long as appropriate \ncredit is given and the new creations are licensed under the identical terms.","source_license":"CC0","license_restricted":false}