Turning Challenges into Success: Successful Pregnancy in Advanced Maternal Age with Adenomyosis Using Prolonged GnRH Agonist Protocol: A Case Report

Introduction

Adenomyosis is a well recognized contributor to reduced success in in vitro fertilization-embryo transfer (IVF-ET) success. Despite numerous proposed strategies, no stimulation approach has consistently and robustly improved outcomes.¹ Prolonged GnRH agonist (GnRHa) protocols have demonstrated favorable effects on IVF outcomes in patients with adenomyosis.^2–4 However, their efficacy in advanced maternal age (AMA) remains uncertain with available studies failed to demonstrate consistent or promising results.⁵ AMA itself has become a critical demographic and clinical challenge, as increasing numbers of women postpone childbearing beyond the age of 35.^6,7 It is associated with diminished ovarian reserve, impaired oocyte quality, and reduced IVF success rates. In addition, AMA women may exhibit relative LH deficiency and premature LH surges, further compromising follicular development and implantation.^1,8

The management of infertility becomes even more complex when AMA coexists with adenomyosis or endometriosis, as these conditions further impair outcomes through altered endometrial receptivity, chronic pelvic inflammation, and disruption of oocyte quality.⁹ In such cases, prolonged GnRHa protocols may offer dual benefits: stabilizing LH dynamics in aging ovaries while simultaneously suppressing adenomyotic and endometriotic activity, thereby creating a more favorable reproductive environment.¹⁰ By achieving deeper pituitary downregulation and more stable hormonal control, prolonged GnRHa pretreatment may enhance both oocyte maturation and endometrial receptivity in this difficult-to-treat population.^9,10

Emerging evidence suggests that prolonged GnRHa protocols may improve oocyte yield and support endometrial receptivity in AMA, though robust data on live birth outcomes remain limited. This highlights the importance of continued evaluation of such strategies.¹¹ Here, we report a case of an AMA patient with adenomyosis and endometriosis, who achieved unexpectedly high mature oocyte yield following a prolonged GnRHa protocol, highlighting its potential role in this challenging population.

Case Presentation

A 41-year-old Indonesian woman, married for thirteen years and nulliparous, presented to our fertility clinic with primary infertility. Her medical history was significant for AMA, posterior adenomyosis (Figure 1), and symptomatic endometriosis previously managed by surgical ablation and excision of superficial lesions across the tubo-ovarian regions, uterine corpus, and peritoneum (laparoscopic surgery performed on December 3, 2024) (Figure 2). Despite prior interventions, her ovarian reserve was within normal limits for age, with anti-Müllerian hormone measuring 2.41 ng/mL both pre- and post-operatively. Her partner was diagnosed with teratozoospermia, as evidenced by sperm analysis showing a normal total count and motility but only 2% normal morphology, contributing a significant male factor to their infertility diagnosis. There was no significant family or psychosocial history.

Figure 1 Transvaginal ultrasound features of posterior adenomyosis. (A) Coronal transvaginal ultrasound demonstrating posterior myometrial heterogeneity and ill-defined thickening without a discrete focal mass. (B) Transvaginal ultrasound showing characteristic adenomyosis features, including subendometrial echogenic lines and buds extending into the posterior myometrium. (C) Sagittal transvaginal ultrasound illustrating asymmetric posterior myometrial wall thickening with increased translesional vascularity on color Doppler, consistent with posterior adenomyosis.

Figure 2 Laparoscopic findings demonstrating superficial endometriosis involving the peritoneum, left ovary, and left ovarian fossa, with red-marked areas indicating the superficial lesions.

Given the challenging context of adenomyosis, endometriosis, AMA, and male factor infertility, a personalized IVF strategy was adopted, employing a prolonged GnRHa protocol aimed at maximizing follicular recruitment and suppressing residual endometriosis activity. Following surgery, the patient received a depot triptorelin acetate 3.75 mg injection on day 2 menstruation, initiating pituitary downregulation for four weeks. Monitoring confirmed complete down-regulation, with a baseline estradiol (E2) of 10.49 pg/mL and endometrial thickness of 3.7 mm. Controlled ovarian stimulation (COS) was then initiated using follitropin alfa 300 IU and lutropin alfa 150 IU (Pergoveris®) during the stimulation phase. On stimulation day (SD) 6, transvaginal ultrasound demonstrated ten developing follicles (six on the left ovary and four on the right, most measuring <11 mm). An additional 75 IU of follitropin alfa was introduced, increasing the daily dose to follitropin alfa 375 IU with lutropin alfa 150 IU. By SD8, follicular growth remained modest (<13 mm), and by SD10 progression had plateaued, necessitating escalation to follitropin alfa 450 IU with lutropin alfa 150 IU. At trigger, the leading follicular diameters measured 15.4–20.5 mm (mean 17.0 mm). At the time of final maturation, E2 was 2903.5 pg/mL and progesterone 0.86 ng/mL. Final oocyte maturation was induced with 250 µg choriogonadotropin alfa (Ovidrel®) (Figure 3). Eight oocytes were retrieved, all underwent intracytoplasmic sperm injection (ICSI), achieving 100% fertilization. Embryo culture was continued to day 3 (D3), yielding seven embryos. Two good-quality D3 embryos were selected for fresh transfer (Figure 4A and B), while the remaining five were cultured to day 5 (D5). Of these, three blastocysts reached sufficient quality, comprising two good-quality and one moderate-quality embryo, which were cryopreserved.

Figure 3 Protocol stimulation chart.

Figure 4 Morphology of the two cleavage-stage embryos selected for transfer on day 3. (A) Embryo 1 at the 7-cell stage with good morphological quality. (B) Embryo 2 at the 7-cell stage with good morphological quality.

The evening after oocyte pickup (OPU), the patient received intensive luteal phase support consisting of hCG 1500 IU every 3 days, vaginal progesterone 400 mg twice daily, oral dydrogesterone 10 mg three times daily, estradiol valerate 2 mg twice daily, and subcutaneous progesterone 25 mg every 3 days, up to 12 weeks of gestation. Serial β-hCG monitoring demonstrated a positive trend, rising from 80 mIU/mL after ET to 1920 mIU/mL one week later, consistent with early pregnancy. The patient was followed with close antenatal surveillance throughout the pregnancy (Figure 5A and B). At the time of reporting, the patient is 35+6 weeks pregnant with a viable singleton fetus; physical examination was unremarkable, with stable vital signs and normal systemic findings.

Figure 5 Antenatal ultrasound surveillance demonstrating fetal well-being. (A) Pulsed-wave Doppler ultrasound confirming a normal fetal heart rate. (B) Three-dimensional (3D) rendered ultrasound at 26 weeks of gestation showing a healthy singleton fetus with normal surface anatomy and no detectable anomalies.

Discussion

This case highlights the potential of prolonged GnRHa protocols to overcome multiple reproductive challenges in women with AMA. The achievement of a clinical pregnancy in a patient with coexisting adenomyosis and endometriosis overcame low expectations and offers important insights into strategies for improving IVF outcomes in complex scenarios. Adenomyosis negatively impacts IVF-ET outcomes through impaired folliculogenesis, distorted pelvic anatomy hindering oocyte retrieval, reduced fertilization potential, and decreased implantation rates due to altered endometrial receptivity.^12,13

Clinical pregnancy rates decline from approximately half in women without ultrasonographic adenomyosis to markedly lower levels in those with severe disease (42.7% vs. 13.0%), highlighting the prognostic impact of disease severity on IVF/ICSI outcomes. Notably, outcomes are further influenced by the frequent coexistence of endometriosis, reported in 33% to 87% of cases, which compounds the negative impact on reproductive prognosis, as illustrated in this case.¹⁴ Adenomyotic lesions are known to express GnRH receptors.³ Prolonged pituitary downregulation with GnRHa protocols induces a hypogonadotropic, hypogonadal state characterized by suppressed E2 levels, depriving lesions of hormonal stimulation.¹² Several studies have reported favorable reproductive outcomes, including clinical pregnancies and live births, in women with adenomyosis following the use of prolonged GnRHa protocols.^15,16

In addition to adenomyosis and endometriosis, AMA is an independent barrier to fertility, primarily due to a decreased ovarian reserve and diminished oocyte quality. Women over 35 experience a significant increase in embryo aneuploidy, with rates reaching up to 90% in their late 40s. The likelihood of producing a euploid blastocyst drops below 5% after the age of 43.¹ Therefore, maximizing ovarian response is crucial for women with AMA, retrieving a larger number of oocytes increases the chances of identifying at least one euploid embryo. The optimal COS response is typically 6–15 oocytes, with LBR maximized at a yield of approximately 15 (12–18).^17–20 Suboptimal retrieval reduces embryo availability, while excessive responses increase the risk of supraphysiologic E2 levels, ovarian hyperstimulation syndrome (OHSS), and impaired endometrial receptivity.^11,21 Our case demonstrated an unexpectedly favourable response, retrieving eight mature oocytes and achieving 100% fertilization, underscoring how individualized strategies can mitigate the cumulative burden of AMA, adenomyosis, and endometriosis. This aligns with recommendations emphasizing tailoring ovarian stimulation protocols to patient-specific prognostic factors to optimize cumulative LBR in AMA patients.^1,22

Conclusion

This case demonstrates that prolonged GnRHa protocols may achieve favorable outcomes in patients with AMA with multiple adverse prognostic factors, including adenomyosis and endometriosis. The achievement of fertilization and ongoing pregnancy in this patient is particularly notable, as these conditions generally result in poor IVF outcomes. While encouraging, such results should be interpreted cautiously, as they may not be generalizable. For patients with adenomyosis and AMA, prolonged downregulation represents a potential strategy to optimize both follicular recruitment and endometrial receptivity. These findings highlight the need for further prospective studies, ideally including preimplantation genetic testing and cumulative LBR as primary endpoints, to clarify the broader applicability of prolonged GnRHa protocols in such complex infertility cases.