Comprehensive Fertility Management After Pituitary Adenoma Surgery: Lessons from a Rural Japanese Case and Practical Review

Abstract

Background and Clinical Significance: Pituitary adenomas, also termed pituitary neuroendocrine tumors, pose a significant risk of hypogonadotropic hypogonadism (HH) after surgical resection, with profound consequences for fertility and sexual function in young patients. Case Presentation: We present the case of a 29-year-old man from rural Japan who developed severe HH and azoospermia following two transsphenoidal resections for a large pituitary adenoma. Despite early engagement with neurosurgery teams, fertility management was delayed by the absence of on-site endocrinology expertise and limited local oncofertility resources. After comprehensive endocrine evaluation and counseling, the patient began combined human chorionic gonadotropin and recombinant follicle-stimulating hormone therapy, resulting in full recovery of sexual function and normalization of semen parameters, ultimately leading to spontaneous conception and the birth of a healthy child. Building on this real-world case, we provide a narrative review of current practical management strategies for HH after pituitary surgery, including the utility of hormone-stimulation tests, Japanese guideline-based subsidy systems, and best-practice approaches to hormonal replacement. Conclusions: This case underscores not only the necessity for early, interdisciplinary collaboration and preoperative counseling but also highlights a rare instance in which a patient with a benign tumor received care that did not address his fertility-related needs, emphasizing that such considerations should be integrated into preoperative counseling even for non-malignant conditions. Strengthening regional oncofertility networks and improving healthcare providers' awareness of fertility-preservation options remain essential for improving outcomes.

Keywords: CNS tumor; PitNET; benign brain tumor; central nervous system; fertility preservation; male infertility counseling; oncofertility care network; reproductive endocrinology; sexual complications of neurosurgery; sperm cryopreservation.

Figure 1

Sequential coronal and sagittal T1-weighted post-gadolinium enhanced magnetic resonance imaging (MRI) images of the hypothalamo-pituitary region before and after two transsphenoidal pituitary tumor resections. (a) MRI obtained 19 days before the initial pituitary tumor resection. A pituitary tumor with marked contrast enhancement is seen in the sella turcica, compressing the optic nerve superiorly. (b) MRI obtained during the interval between the initial and second pituitary tumor resections (7 days after the initial resection). Compression of the optic nerve by the tumor has been relieved, although residual tumor tissue remains, predominantly on the left side. (c) MRI obtained 400 days after the second pituitary tumor resection. The tumor has been completely resected, with no evidence of recurrence during follow-up.

Figure 2

Timeline from the diagnosis of pituitary adenoma at a regional hospital through referral to our institution for specialized treatment, initiation of hormone therapy, and eventual live birth. The upper timeline illustrates the patient’s clinical course from initial diagnosis and referral through advanced treatment and achievement of pregnancy; Below the timeline, the dosages and timing of hormone replacement therapy—specifically human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (rFSH)—are shown, along with corresponding semen-analysis results, serum-sex-hormone concentrations, and changes in sexual function; Semen volume and sperm concentration are presented as both numerical values and bar graphs (reference values: ≥1.6 mL for semen volume, ≥16 × 106/mL for sperm concentration), while sperm motility is shown numerically only (reference value: ≥42%); Total testosterone levels are presented both numerically and as bar graphs (reference interval: 1.31–8.7 ng/mL), whereas estradiol concentrations are presented numerically only (reference interval: 14.6–48.8 pg/mL). Once both total testosterone and estradiol levels exceed the assay detection limits, the ratio of total testosterone (converted from ng/mL to ng/dL) to estradiol (pg/mL) is calculated and displayed as the T/E ratio; Sexual function is indicated by the Erection Hardness Score (EHS), graded on a four-point scale (1 = lowest, 4 = highest).

Figure 3

Images of the genitalia just before initiation of hormone replacement therapy after two pituitary resections. Color Doppler ultrasonography showing longitudinal sections of the testicular parenchyma ((a) right testis, (b) left testis). Sagittal T2-weighted image of pelvic organs on plain MRI (c).