To evaluate the effectiveness of GnRH agonist and combined oral contraceptives protocols in Intracytoplasmic Sperm Injection (ICSI) cycles for patients with different stages of endometriosis

Background: Endometriosis, a chronic gynecological condition affecting reproductiv e-age women, is strongly associated with infertility. Gonadotropin -releasing hormone agonists (GnRH -a) are widely used for endometriosis management and may improve outcomes in assisted reproductive technology (ART). This study to assess the reproductive ou tcomes of endometriosis patients undergoing controlled ovarian stimulation and ICSI cycles with two treatment regimens: GnRH agonists and combined oral contraceptives (COCs).

It is a prospective study conducted from March 2020 to March 2024. A total of 100 patients with stage I–IV endometriosis were randomly assigned to two treatment groups: a GnRH agonist group ( N=50) and a combined oral contraceptive (COC) group ( N=50). Clinical, hormonal, and reproductive parameters were assessed and compared between the groups.

The GnRH agonist group demonstrated superior reproductive outcomes compared to the COC’s group, with higher clinical pregnancy rates (76% vs. 72%), ongoing pregnancy rates (68% vs. 56%), and cumulative live birth rate per patient (50% vs. 46% for stage I –II and 40% vs. 38% for stage III –IV). Although the GnRH agonist group required higher gonadotropin doses, they exhibited improved embryo quality and implantation success. Additionally, miscarriage rates were lower in the GnRH agon ist group (6% vs. 12%) compared to COC’s group

Both regimens were effective in enhancing reproductive outcomes, however, the GnRH agonist protocol was associated with higher clinical pregnancy and live birth rates, particularly in patients with advanced-stage endometriosis. The administration of GnRH agonists in patients with varying stages of endometriosis may enhance ICSI outcomes compared to the COC protocol. Optimizing treatment strategies is essential to improving reproductive outcomes in endometriosis-associated infertility. These findings highlight the importance of tailored treatment protocols to enhance reproductive success in endometriosis patients undergoing ART.

Endometriosis, GnRH agonists, ICSI, ART, enhancing reproductive, endometriosis patients

Endometriosis is a common gynecological disorder characterized by the growth of tissue similar to the endometrium outside of the uterus [1]. It affects 6% to 11% of women of reproductive age, often leading to symptoms such as dyspareunia, dysmenorrhea and infertility, and is observed in up to 50% of women experiencing infertility [2]. The primary symptoms of endometriosis include chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility [3]. It is a multifacto rial disease that directly impairs fertility by disrupting the normal anatomy of the fallopian tubes and ovaries. Indirectly, it contributes to infertility through inflammatory responses and oxidative stress, which can compromise oocyte quality [4]. Laparoscopy is a gold standard method to be performed to obtain a definitive diagnosis of endometriosis based on pathology seen and obtained at the time of surgery [5]. The administration of a GnRH agonist in the postoperative setting aims to eradicate microscop ic endometriotic lesions that may not be visualized or resected during surgery, while also inhibiting the development of new lesions [6]. Patients with suspected early -stage endometriosis are initially managed with medical therapy, including oral contracep tives and nonsteroidal anti - inflammatory drugs (NSAIDs) [7]. International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 29 ~ For cases where pain persists despite first -line treatment, gonadotropin-releasing hormone (GnRH) analogues are considered a second-line therapeutic option [8]. Gonadotropin-releasing hormone a gonists (GnRHa) are widely used in the management of endometriosis. These synthetic analogs of gonadorelin, a hypothalamic hormone, initially stimulate the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which re gulate ovarian production of estrogen and progesterone, key hormones in the menstrual cycle [9]. GnRH -a competitively binds to GnRH receptors in the pituitary gland, inhibiting the release of endogenous GnRH. This suppression results in decreased ovarian h ormone secretion, effectively inducing pituitary down regulation [10]. Additionally, GnRH -a, prevents premature luteinization of follicles, enhancing follicular synchronization and development. It also mitigates inflammatory responses, optimizes the pelvic microenvironment, and improves oocyte and embryo quality [11]. GnRH-a can effectively prevent premature luteinization of follicles, promoting better synchronization of follicular growth and development. GnRH Agonist Long Protocol (Depot) All 50 women wil l receive three Zoladex 3.65 mg injections subcutaneously (SC). The injections are given either as a single dose or divided into two doses, 6 weeks apart. After the Zoladex injections, controlled ovarian stimulation (COS) will be initiated. All patients were informed of the potential side effects associated with GnRH -a therapy, including hot flushes, depression, vaginal dryness, and mild but reversible bone loss. GnRH-a, was administered monthly for a total of five or six cycles. The dosage of FSH will be i ndividually determined for each woman. GnRH antagonist will be given if needed during the ovarian stimulation phase. Ovum pickup will be performed. Four months after the protocol initiation, women are scheduled for an appointment at the IVF department. Women are scheduled for an appointment precisely 28 days after the last Zoladex injection for further assessment. Full suppression will be done during this appointment. Ovarian stimulation is commenced with subcutaneously injected gonadotropins (FSH). The pro tocol concludes with Frozen Embryo Transfer (FET). Combined Oral Contraceptives In the Combined Oral Contraceptives (COC) group, all 50 women will undergo a three -month treatment with continuous COC therapy, typically with ethinyl estradiol/levonorgestre l 30/150μg, or other one -phase sub -50 OCs if previously used. After completing the COC regimen, women are instructed to contact the IVF department on the first day of withdrawal bleeding. On the second day of bleeding, they will visit the IVF center to ini tiate suppression of the luteinizing hormone (LH) peak. Ovarian stimulation with subcutaneous gonadotropins (FSH) will begin one day later, with dosage individualized for each patient. Outcomes of IVF/ICSI cycles with COH protocols including GnRH agonists and COC were analyzed among the study groups. Methodology It is a prospective study which was conducted between March 2020 and March 2024 and included 100 infertile women diagnosed with different stages of endometriosis confirmed by laparoscopy and divide d into two groups. First group GnRH agonist ( N=50) and COC’S ( N=50). All participants were undergoing intracytoplasmic sperm injection (ICSI) cycle at MHRT Hospital and Research Center, Hyderabad, Telangana, India. The study was approved by the Institution al Ethics Committee. Informed consent was obtained from all participants, permitting the collection and analysis of their clinical and laboratory data, including medical history, for the purpose of clinical. The study included patients who met the followi ng inclusion criteria  Women under the age of 40 with a confirmed diagnosis of endometriosis, either through laparoscopic evaluation and surgical resection performed at least one year prior to study enrollment or the presence of ovarian endometriotic cysts identified via ultrasound at the start of the study  A body mass index (BMI) of less than 28 kg/m²  A diagnosis of infertility with an indication for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Endometriosis was classified based on the ASRM guidelines, all patients were followed up through the completion of surgical procedures, postoperative GnRH -a therapy, up to three ART cycles, and a four-week follow-up period. Statistical Analysis A comparative analysis was conducted betwee n the two groups receiving different stimulation protocols. Continuous variables were analyzed using one -way ANOVA, while categorical variables were assessed with the Chi -square test. Pre-stimulation cycle characteristics were evaluated using the Kruskal -Wallis H- test for continuous variables and Pearson's Chi-square or Fisher's exact test for categorical variables. All statistical tests were two - tailed, with a significance level set at p<0.05. A 95% confidence interval was used, and all statistical analyse s were performed using SPSS version 23.0. Assisted Reproductive Technologies In patients who underwent surgery, ovarian stimulation commenced following down -regulation with 0.1 mg of GnRH -a using the long protocol. Daily subcutaneous injections of GnRH - a (Decapeptyl 0.1; Ferring, Kiel, Germany) were initiated on cycle day 18. Beginning on day 3 of the subsequent cycle, recombinant FSH (Gonal -F; Serono) was administered daily at doses ranging from 150 IU to 300 IU. Ovulation was triggered with 10,000 IU of hCG (Pregnesin; Serono), and ultrasonography-guided follicular puncture was performed 35 to 36 hours post-trigger. In patients who received GnRH -a treatment, ovarian stimulation commenced exactly two weeks after the final depot injection of GnRH-a, with daily subcutaneous administration of recombinant FSH (Gonal-F; Serono) at doses ranging from 150 IU to 300 IU. The subsequent treatment protocol, including ovulation induction, follicular puncture, and luteal phase support, followed the same procedure as des cribed previously. A maximum of three IVF/ICSI cycles were included in the analysis. Assessment of Pregnancy Fourteen days after Embryo Transfer (ET), pregnancy was assessed through a β -hCG assay and endometrial thickness measurement. Only clinical pregnancies were recorded, defined by rising β-hCG levels and confirmed ultrasonography detection of an amniotic sac.

A total of 100 eligible p atients were enrolled and included in the study. Patients were randomized into two groups patients with International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 30 ~ stage I–II endometriosis-GnRH agonist (N= 16), COCs (N= 21) and stage III -IV endometriosis GnRH agonist (N= 34), COCs (N= 29). The Figure 1 of this stud y evaluated 100 endometriosis patients, comparing two treatment protocols. Group 1 (GnRH agonist long protocol, N=50) included 19 fresh embryo transfers (ET) and 31 frozen -thawed ET, resulting in 5 biochemical pregnancies, 38 clinical pregnancies, 34 ongoi ng pregnancies, and 32 live births -20 in patients with minimal to mild endometriosis and 12 in those with moderate to severe endometriosis. Group 2 (combined oral contraceptives, N=50) had 16 fresh ET and 34 frozen -thawed ET, yielding 4 biochemical pregnan cies, 31 clinical pregnancies, 28 ongoing pregnancies, and 16 live births -11 in minimal to mild endometriosis and 5 in moderate to severe cases. These findings demonstrate the efficacy of both regimens in enhancing reproductive outcomes, with success varyi ng according to endometriosis severity. The Table 1 in this study illustrates the socio -demographic and clinical profiles of endometriosis patients treated with GnRH agonists (N=50) and Combined Oral Contraceptives (N=50) were compared. The GnRH agonist gr oup had a mean age of 32.22±4.42 years, BMI of 23.3±2.9 kg/m², and lower AMH (0.91±1.1 ng/ml) and AFC (4 [3–4]). A higher proportion of patients in this group had ASRM stage III-IV (68%) and primary infertility (29). In contrast, the Combined Oral Contrace ptives group had an average age of 33.41±3.42 years, lower BMI (22.42±2.78 kg/m²), and higher AMH (2.52±3.8 ng/ml) and AFC (5 [6–8]). This group had a higher incidence of secondary infertility (36%) and more patients with ASRM stage I -II (42%). Both groups had similar infertility durations, but the GnRH agonist group had more previous failed cycles and a higher proportion of nulliparous patients. In the Table 2 shows the comparative study of Controlled Ovarian Stimulation (COS) and intracytoplasmic sperm injection (ICSI) cycles in endometriosis patients using a GnRH agonist protocol versus a combined oral contraceptive (COC) protocol, several key outcomes were assessed. The total dose of gonadotropins was significantly higher in the GnRH agonist group (2700. 0 IU [2250.0 -3440.6 IU]) compared to the COC group (2400.0 IU [1846.9 -3075.0 IU]). Both groups received similar doses of LH (GnRH agonist: 1093.3±458 IU, COC: 1089.5±314.6 IU), while the total FSH dose was markedly higher in the COC protocol group (3612±22 72.8 IU) compared to the GnRH agonist group (595.13±2158.7 IU). The duration of gonadotropin stimulation was similar in both groups, with an average of 11±2 days. Endometrial thickness on the trigger day was significantly thinner in the GnRH agonist group (3.58±1.73 mm) compared to the COC group (5.53±3.42 mm). Serum estradiol levels on the hCG trigger day were significantly lower in the GnRH agonist group (1832.2±889.6 pg/mL) compared to the COC group (2200.9±806.9 pg/mL). In terms of oocyte retrieval, t he GnRH agonist group yielded a higher number of oocytes per patient (5 [3 -6] vs. 4 [3-5]), with a higher number of mature oocytes (MII) retrieved (4 [3-5] vs. 3 [3- 5]) in comparison to COC group. The number of immature oocytes (MI + PI) retrieved was simi lar in both groups (GnRH agonist: 2 -3 [1 -3], COC:2) [1-3]. Fertilization rates were comparable between the groups, with the GnRH agonist group fertilizing 4 oocytes (2 -4) per patient and the COC group fertilizing 3 oocytes (2 -3). Both protocols produced si milar numbers of blastocysts, with the GnRH agonist group generating 1 (1 -2) blastocyst per patient and the COC group generating 1 (0-1) blastocyst per patient. These findings indicate that while differences exist in gonadotropin dosing and ovarian respons e between the two protocols, fertilization and blastocyst formation rates were similar in both groups. In this study, reproductive outcomes were evaluated in 100 Endometriosis patients (N=50 per group) treated with either GnRH agonist or Combined Oral Cont raceptives (COC) protocols. For fresh single embryo transfer (SET), the success rate for patients with Stage I -II endometriosis was 12% (6/50) in the GnRH agonist group and 14% (7/50) in the COC group. For Stage III-IV endometriosis, the success rates were 6% (3/50) for GnRH agonists and 8% (4/50) for COC. In frozen single embryo transfer (FET), success rates in Stage I -II endometriosis were 48% (24/50) for GnRH agonist and 52% (26/50) for COC, while for Stage III -IV endometriosis, the success rates were 34 % (17/50) for GnRH agonist and 26% (13/50) for COC. The biochemical pregnancy rates were similar between the two groups, with 10% (5/50) in the GnRH agonist group and 8% (4/50) in the COC group. The clinical pregnancy rate (CPR) was 76% (38/50) in the GnRH agonist group and 72% (36/50) in the COC group, while ongoing pregnancy rates were 68% (34/50) and 56% (28/50), respectively. The miscarriage rate per pregnancy was lower in the GnRH agonist group (6%) compared to the COC group (12%). CPR per started cycl e was 46% (23/50) for GnRH agonist and 34% (17/50) for COC. Cumulative CPR per patient was 38% (19/50) for GnRH agonist and 40% (20/50) for COC. The cumulative live birth rates per patient were comparable between the two groups, with 50% (25/50) for Stage I-II endometriosis and 40% (20/50) for Stage III-IV endometriosis in the GnRH agonist group, and 46% (23/50) and 38% (19/50), respectively, in the COC group. Statistical analysis In the Table 3, Depicts Reproductive outcomes in endometriosis patients treated with GnRH agonists (N=50) or Combined Oral Contraceptives (N=50) protocols were evaluated. In fresh single embryo transfer (SET) cycles, the success rate for patients with Stage I -II endometriosis was 12% (6/50) in the GnRH agonist group and 14% (7/50) in the COC group. For Stage III -IV endometriosis, the success rates were 6% (3/50) for GnRH agonists and 8% (4/50) for COC (Figure 2). For frozen SET, success rates in Stage I -II endometriosis were 48% (24/50) for GnRH agonist and 52% (26/50) for COC, wh ile for Stage III -IV endometriosis, the success rates were 34% (17/50) for GnRH agonist and 26% (13/50) for COC (Figure 3). The biochemical pregnancy rates were similar between the two groups, with 10% (5/50) in the GnRH agonist group and 8% (4/50) in the COC group. The clinical pregnancy rate (CPR) was 76% (38/50) in the GnRH agonist group and 72% (36/50) in the COC group, while ongoing pregnancy rates were 68% (34/50) and 56% (28/50), respectively. The miscarriage rate per pregnancy was lower in the GnR H agonist group (6%) compared to the COC group (12%). CPR per started cycle was 46% (23/50) for GnRH agonist and 34% (17/50) for COC. Cumulative CPR per patient was 38% (19/50) for GnRH agonist and 40% (20/50) for COC. The cumulative clinical pregnancy ra te per patient was 62% for the GnRH agonist group, versus 54% for the Combined Oral Contraceptives group. Furthermore, the cumulative live birth rate was significantly higher in the GnRH agonist group, with 50% in Stage I -II and 40% in Stage III -IV, compar ed to 46% and 38%, respectively, in the Combined Oral Contraceptives group (Figure 4). These findings underscore the superior reproductive outcomes associated with GnRH agonist treatment in endometriosis patients.

This study evaluated the reproductive outcomes of two treatment regimens-GnRH agonists and Combined Oral Contraceptives International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 31 ~ (COCs) in patients with endometriosis. The GnRH agonist group exhibited lower AMH and AFC levels, reflecting a diminished ovarian reserve, which aligns with the ovari an suppression commonly seen in both endometriosis sand GnRH agonist treatment. The reduction in AMH levels indicates a loss of follicular reserve, particularly in women with advanced endometriosis (Stage III -IV), where ovarian damage is frequently observe d. The COCs group demonstrated higher AMH and AFC levels, indicating a better ovarian reserve and less ovarian dysfunction. Elevated AMH is correlated with enhanced fertility potential which may explain the higher prevalence of secondary infertility (36%) and Stage I -II endometriosis (42%) in this group -conditions generally associated with more favorable fertility outcomes. Secondary infertility in these women is more likely attributed to factors such as fallopian tube function or luteal phase abnormalities, rather than ovarian dysfunction [12]. The greater proportion of Stage I-II patients in the COCs group suggests that infertility may primarily result from other factors, including pelvic adhesions or alterations in the endometrial environment. Nulliparous women with endometriosis often experience more severe infertility due to the prolonged effects of the disease, such as pelvic adhesions and compromised oocyte quality [13]. The greater number of previous failed cycles in the GnRH agonist group suggests mo re severe or resistant infertility, which likely contributed to less favorable ART outcomes. While GnRH agonist therapy can enhance fertility by reducing inflammation and creating a more favorable hormonal environment [14], the severity of the disease and the presence of prior failed cycles may still limit reproductive success. The GnRH agonist group required higher doses of gonadotropins (2700.0 IU vs. 2400.0 IU) and FSH (595.13±2158.7 IU vs. 3612±2272.8 IU) compared to the COCs group. Despite these differences, the stimulation durations were similar between both groups (11±2 days), suggesting that GnRH agonist therapy required a more intensive stimulation protocol to achieve a comparable ovarian response. The COCs group demonstrated significantly thicker e ndometrial linings (5.53±3.42 mm vs. 3.58±1.73 mm) and higher serum estradiol levels on the hCG trigger day (2200.9±806.9 pg/mL vs. 1832.2±889.6 pg/mL), which corresponds with the established role of COCs in promoting endometrial receptivity by maintaining stable hormonal levels [12]. In contrast, GnRH agonists induce a hypo -estrogenic state, leading to thinner endometrial linings, which may compromise implantation success [14]. The GnRH agonist group retrieved slightly more oocytes (4 vs. 3), with compara ble numbers of mature oocytes (MII) in both groups. The GnRH group had a higher incidence of immature oocytes (2 -3 vs. 2), likely due to COCs' suppressive effect on ovarian function [13]. Additionally, the GnRH agonist group had more fertilized oocytes (4 vs. 3), suggesting better fertilization outcomes despite a thinner endometrial lining. Both groups produced a similar number of embryos (3), indicating comparable effectiveness in embryo production despite differences in ovarian stimulation and endometrial response. In fresh single embryo transfer (SET) cycles, the success rate for patients with Stage I -II endometriosis was 12% (6/50) in the GnRH agonist group and 14% (7/50) in the COC group. For Stage III-IV endometriosis, the success rates were 6% (3/50) for GnRH agonist and 8% (4/50) for COC [14] For frozen SET, success rates in Stage I -II endometriosis were 48% (24/50) for GnRH agonist and 52% (26/50) for COC, while for Stage III -IV endometriosis, the success rates were 34% (17/50) for GnRH agonist and 2 6% (13/50) for COC. These findings align with previous research suggesting that GnRH agonists may optimize the ovarian environment, improving embryo implantation and mitigating the impact of endometriosis on fertility [15]. Additionally, the GnRH agonist g roup had lower miscarriage rates (6%) compared to the COCs group (12%), highlighting the treatment's role in enhancing reproductive outcomes. The cumulative clinical pregnancy rate per patient was significantly higher in the GnRH agonist group (38%) compar ed to the COCs group (40%), with notably higher live birth rates in Stage I-II (50% vs. 46%) and Stage III -IV (40% vs. 38%) for the GnRH agonist group in comparison to the COC’s group. These

further support the evidence that GnRH agonist therapy not only enhances short -term pregnancy outcomes but also promotes long -term fertility success in women with endometriosis [12]. The improved outcomes in the GnRH agonist group, especially in advanced stages of endometriosis, highlight the potential of GnRH agonists to alleviate the effects of severe disease, such as pelvic adhesions and ovarian dysfunction, which can negatively affect fertility [15]. These findings align with previous prospective studies showing the beneficial impact of GnRH agonists on fertility in patients with endometriosis [13]. Table 1: Socio-demographic characteristics and clinical profiles from Endometriosis patients with GnRH agonist and combined oral contraceptives protocol Clinical characteristics GnRH agonist (N=50) Combined Oral Contraceptives Protocol (N=50) P-Value Patient age (years) 32.22±4.42 33.41±3.42 0.13 BMI (kg/m2) 23.3 ± 2.9 22.42± 2.78 0.12 AMH (ng/ml) 0.91±1.1 2.52±3.8 0.004 Subfertility Primary Infertility Secondary Infertility 29(58%) 21(42%) 36(72%) 14(28%) 0.20 Baseline AMH 1.19 (1– 1.26) 1.52(1– 1.49) AFC 4(3-4) 5 (6-8) 1.00 Basal FSH (IU/L) 8.01 ± 1.91 7.21 ±1.92 0.03 Duration of infertility (years) 2.82 ±1.6 2.5 ±1.2 0.26 ASRM stage I-II 16(32%) 21(42%) 0.40 ASRM stage III-IV 34(68%) 29(58%) Previous failed Cycles 0 13(26%) 22(44%) 0.26 1 20(40%) 16(32%) >2 17(34%) 12(24%) Parity 0 26(52%) 18(36%) 0.15 1 24(48%) 32(64%) International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 32 ~ Table 2: Controlled ovarian stimulation and ICSI cycles in Endometriosis patients with GnRH agonist and combined oral contraceptives protocol Variable GnRH agonist (N=50) Combined Oral Contraceptives Protocol (N=50) P-Value Total dose of gonadotropins 2700.0 (2250.0-3440.6) 2400.0 (1846.9-3075.0) 0.001 Total dosage of FSH (IU) 595.13±2158.7 3612±2272.8 0.001 Total dosage of LH (IU) 1093.3±458 1089.5±314.6 0.91 Duration of Gonadotrophin stimulation (days) 11±2 11±2 1.00 Endometrial thickness(mm) 3.58± 1.73 5.53 ±3.42 0.0005 Serum 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 Total number of oocytes retrieved per patient 5(3-6) 4(3-5) 1.00 No of Mature Oocytes retrieved (MII) per patient 4(3-5) 3(3-5) 1.00 No of Immature oocytes (MI+PI) per patient 2-3(1-3) 2(1-3) 0380 No. of oocytes fertilized per patient 4(2-4) 3(2-3) 1.00 Total number of Blastocysts per patient 1(1-2) 1(0-1) 0.51 Table 3: Reproductive outcomes of cycles in endometriosis patient groups and combined oral contraceptives protocol Variable GnRH agonist (N=50) Combined Oral Contraceptives Protocol (N=50) P-Value Fresh Single Embryo Transfer Stage I-II 6/50(12%) 7/50(14%) 1.00 Stage III-IV 3/50(6%) 4/50(8%) 1.00 Frozen Single Embryo Transfer Stage I-II 24/50(48%) 26/50(52%) 0.81 Stage III-IV 17/50(34%) 13/50(26%) 0.51 Biochemical pregnancy 5/50(10%) 4/50(8%) 1.00 Clinical Pregnancy Rate (CPR) 38/50(76%) 36/50(72%) 0.81 Ongoing Pregnancy 34/50(68%) 28/50(56%) 0.30 Miscarriage Rate per Pregnancy 3/50 (6%) 6/50 (12%) 0.48 CPR per Started Cycle 23/50 (46%) 17/50 (34%) 0.30 Cumulative CPR per Patient 19/50 (38%) 20/50 (40%) 1.00 Cumulative Live Birth Rate per patient Stage I-II 25/50(50%) 23/50(46%) 0.84 Stage III-IV 20/50(40%) 19/50(38%) 1.00 Fig 1: Details of the flowchart illustrating participant progression and outlining the primary reproductive outcomes of the enrolled patients. GnRHa, gonadotropin-releasing hormone agonist, combined oral contraceptives International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 33 ~ Fig 2: Illustrates the fresh single embryo transfer (SET) process in Stage I-II and Stage III-IV, comparing the use of GnRH agonists and combined oral contraceptives (COCs) Fig 3: Illustrates the Frozen single embryo transfer (SET) process in Stage I-II and Stage III-IV, comparing the use of GnRH agonist and combined oral contraceptives (COCs).

This study highlights the effectiveness of both GnRH agonist and Combined Oral Contraceptive (COC) protocols in managing endometriosis-related infertility. While GnRH agonists resulted in higher oocyte yield and clinical pregnancy rates in moderat e to severe endometriosis, COC protocols showed comparable outcomes in minimal to mild cases with fewer side effects and lower gonadotropin requirements. Frozen Embryo Transfer (FET) outcomes were generally superior across both groups. These findings under score the importance of individualized treatment strategies based on endometriosis stage and patient profile to optimize assisted reproductive outcomes, offering valuable insights for clinicians in tailoring fertility treatment plans. Disclosure Statement Authors have no competing interests to declare. Acknowledgments We acknowledge all the authors of the manuscript Conflict of Interest Not available Financial Support Not available

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