Secondary male factor infertility after Roux-en-Y gastric bypass for morbid obesity: Case report

Abstract

Surgical treatments such as the Roux-en-Y gastric bypass operation result in the successful treatment of morbid obesity; however, this type of operation may cause long-term side effects due to the reduced absorption of nutrients. Here, we present data suggesting that this operation can result in secondary infertility in males. Six healthy, previously fertile male subjects presented in our centre for secondary infertility after a Roux-en-Y gastric bypass operation for morbid obesity. Reproductive function was assessed with a series of spermiograms, and by testicular biopsy. Secondary azoospermy with complete spermatogenic arrest was diagnosed. The results suggest that weight reduction surgery may cause reproductive dysfunction.

Introduction

The incidence of morbid obesity in the developed world is increasing and may be caused by both dietary and genetic factors (World Health Organization, 1997). Where other treatments have failed, surgical procedures such as the Roux-en-Y gastric bypass operation have been applied successfully to treat this condition (Buchwald and Rucker, 1984). This operation results in a limited gastrectomy which is then attached to the distal small intestine, bypassing the duodenum and proximal small intestine. The effect of the operation is to drastically reduce the absorption of nutrients and therefore reduce weight. Although this operation is highly successful in reducing weight in morbidly obese patients, the malabsorption of nutrients may lead to short- and long-term effects on the body (Kremen et al., 1954; Payne et al., 1963).

Case reports

Between 2001 and 2003, a series of six male subjects presented in the Assisted Reproduction centre in Naples, Italy for secondary infertility. All males had a reproductive history of one child with the present partner prior to the operation (Table I). The patients had undergone a Roux-en-Y gastric bypass operation in different centres in Italy for morbid obesity (body mass index >40 kg/m²) without reported post-operative complications. Subsequent to the successful outcome of this operation, all subjects reported a consistent weight loss of 60–80 kg (76.8±12.3 kg, mean±SD, n=6). Subjects presenting to the centre had a healthy appearance, were on a normocaloric diet including supplementation for iron, calcium, vitamin B12 and folate, and did not report any symptoms suggesting poor health. Blood analyses for glucose, urea, γ-glutamine transferase, transaminases and creatinine did not reveal any signs of physiological problems. The mean age of the patients at presentation in our centre was 38.3±2.4 years (mean±SD, n=6). All patients were characterized by normal levels of FSH (5.0±1.4 mIU/ml, mean±SD, n=6), LH (9.0±3.9 mIU/ml, mean±SD, n=6), total and free testosterone (total testosterone 435±209 ng/ml, mean±SD, n=6; free testosterone 119±40 pg/ml, n=6, normal range 80–146 pg/ml according to laboratory) and sex hormone-binding globulin (32±16 mg/l, n=6, normal range 10–73 mg/l according to laboratory). The time between the operation and presentation for the first consultation in our centre was 16.8±3.9 months (mean±SD, n=6). Couples had been trying to conceive for at least 8 months before presenting to the fertility clinic. All patients signed an informed consent form; however, internal review (IRB) board approval was not sought for the present work because the work was formulated during routine clinical assessment of the patients.

We performed a total of 22 spermiograms (3.7±0.5 analyses per patient, mean±SD, n=6) on these subjects at different intervals during a period of 12–15 months. None of these spermiograms revealed the presence of any spermatozoa, and secondary azoospermy was therefore suspected. Although obstructive azoospermy could not be excluded, the fact that all individuals had previously fathered children indicated non-obstructive azoospermy. We therefore suggested a testicular biopsy in order to perform a histological examination of the testicles. In all cases of testicular biopsy, spermatozoa were absent. Histological analysis of specimens of this testicular tissue from the patients demonstrate spermatogenic arrest at the spermatogonium stage. Patients were characterised with spermatogenic arrest at the Ap stage of sperma-togonia with variable numbers of Ap spermatogonia per patient.

Conclusions

The Roux-en-Y gastric bypass operation is a successful treatment for morbid obesity, and results in the sustained loss of a large proportion of excess weight in these patients. However, the severe reduction in the absorption of nutrients caused by this operation does potentially cause short- and long-term problems for the patient. Although nutritional and pharmacological therapies help relieve some of the short-term difficulties, we present data here suggesting that effects on the male reproductive system persist after the operation. In this report, we document a series of six patients presenting in our centre for secondary infertility with a history of fatherhood prior to Roux-en-Y gastric bypass. After the operation, all patients were characterized by non-obstructive azoospermy with complete spermatogenic arrest, despite the healthy appearance and normal sex hormone profiles. These data suggest that a developmental block of spermatogenesis occurred at a point not related to the action of sex hormones on the testis. The data indicate that either the absorption of nutrients required for spermatogenesis was insufficient in these patients, or that the effect on the reproductive system was non-reversible. We have no data currently on the effects of these operations on female fertility.

In conclusion, although the number of patients is small, and the time scale of the present report is limited, the report suggests a correlation between the Roux-en-Y gastric bypass operation and secondary male factor infertility. A more extensive long-term study should be performed to determine whether these effects are permanent, or a temporary effect due to the surgical procedure. However, we suggest that bariatric surgeons give extensive consultation on the possible short- or long-term effects of Roux-en-Y gastric bypass on the reproductive system, and cryopreservation of semen samples could be offered prior to the operation. Alternatively, it is possible that a nutritional therapy can be developed to counteract these effects.

We thank Vincenzo Monfrecola for his technical contribution to this work.

References

Author notes

1Centre for Reproductive Biology, Clinica Villa del Sole, Via Manzoni, 15 and 2Facolta di Medicina e Chirurgia, II Università degli Studi di Napoli, Via Costantinopoli, 16, 80126 Naples, Italy