madman
Super Moderator
Abstract
Purpose We compared our clinical experience to international standards, assessed by response to treatment and pregnancy rates to ensure our results were comparable.
Methods Men presenting with azoospermia related to hypogonadism were recruited into a treatment program that was managed by one person over 8 years in a secondary care facility. Treatment followed published management plans using urinary gonadotropins. Data were collected on success rates in spermatogenesis, as well as variables that might predict success, and costs. Statistical analysis used non-parametric methods.
Results Of 16 men with HH, 14 achieved spermatogenesis, and 9 had sperm cryopreserved. Of those 14, 6 were successful in achieving a pregnancy with their partner from assisted conception (including ICSI) and one after natural conception. Factors identified to identify men likely to be successful in treatment were whether the testicular volume was larger at the onset of gonadotropins (median 10 mL) with a trend towards greater success if the cause developed after puberty. Mean treatment costs per man treated amounted to GP£4379/UD$5377 (figures for September 2020).
Summary Success rates from this treatment should exceed 70% in most clinical settings. The likelihood of success improves when testicular volume exceeded 10 mL at the initiation of treatment and a trend exists whereby success is more likely whereby when hypogonadism developed after puberty. Treatment costs are at a level likely to benefit the quality of life, supporting the delivery of this treatment, and where necessary and possible, funding is in line with other fertility treatments. This treatment should be available much more widely as a management option for men with hypogonadism, allowing them to father a biological child, rather than using donor sperm.
Introduction
Disorders of sperm function and production are found in 36% of the infertile population [1], but related endocrine causes are rare. One large cohort study of men with sperm disorders found that only 18 of 1035 men (1.7%) had a “clinically significant” endocrine disorder [2]. Severe forms of endocrine-related sperm production disorders include those dysfunctions of the hypothalamic-pituitary axis which result in hypogonadotropic hypogonadism, either are related to anosmia (Kallmann syndrome) or are idiopathic (IHH). Hypogonadotropic hypogonadism is rare, occurring in fewer than one man in 500 [1]. In the paper referred to above, hypogonadotropic hypogonadism was the cause of the man’s infertility in only 2 of the 1035 (0.3%) [2]. This condition is therefore rare but amenable to long-established, effective treatment, by regular gonadotropin injections, usually self-administered [3]. But what is the cost of this treatment and … do some clinics shy away from treating men with IHH because of cost?
Response to treatment is related to the underlying cause of HH: men with postpubertal acquired HH have the best response to treatment and achieve higher pregnancy rates [4]. Combined (hCG and FSH) gonadotropin use treats both hypothalamic and primary pituitary causes of HH and may require quite prolonged stimulation, up to 24 months [5]. Other predictors of a positive response to treatment include larger baseline testicular size and absence of undescended testes. Negative predictors for response to treatment include smaller testicular volume and pubertal status [6].
Our clinical work is undertaken in a secondary care hospital, not in a specialist unit, and we wanted firstly to ensure our results were comparable with national and international standards, secondly to consider if there were any predictive factors evident between the successful and unsuccessful groups and finally to estimate the cost for the treatment. Published literature suggests that 60–75% of men should have sperm (> 1.5 × 106 sperm/mL) on completion of treatment—that is, after 6 months [5, 7]. The aim of treatment in our unit is to induce sufficient numbers of sperm so as to allow sperm to be stored and used at a later date, with the expectation that would be using in vitro fertilization associated with intracytoplasmic sperm injection.
Methods
We used a treatment approach in line with published effective protocols [5, 7]. These involve hCG injections (2000 IU IM) three times a week followed by serum testosterone measured at 4 weeks. Once serum testosterone exceeded 10 nmol/L (288 ng/dL) in line with other published studies [5, 7], the follicle-stimulating hormone was added (FSH 75 IU SC) three times a week. Different proprietary formulations of hCG and FSH injections were used throughout the span of the review—generally the least expensive that the hospital pharmacy could purchase, and generally a urinary derived gonadotropin product. The seminal fluid analysis was performed 4 months after commencing FSH treatment. If there were no sperm present, the dose of FSH was increased to 150 IU SC three times a week, and a further sample assessed 4 months later. Once sperm were observed in the sample, arrangements were made for sperm to be freeze stored. If sperm were not seen on the second sample, gonadotropin therapy was discontinued.
Discussion
The data in this paper are small and might be dismissed as a result, this being seen as a weakness. However, they are data from one clinical service in a teaching hospital, not from a specialist fertility center, and not from a research program, offering gonadotropin therapy for spermatogenesis for over 15 years. This review of the outcomes from our clinical service affirms the importance and effectiveness of spermatogenesis as a treatment and supports the provision of gonadotropin induction of spermatogenesis in a secondary care setting and shows that these patients do not have to be managed in a tertiary fertility unit.
Spermatogenesis was achieved in 14 of 16 men (88%); this compares well with published data in which rates of 60– 75% were achieved with gonadotropin therapy [5, 7]. Larger initial testicular volumes were more likely to lead to success at spermatogenesis, as others have found [6]. We found a trend whereby successful treatment was more likely in men with post-pubertal hypogonadism causes, while others found no difference in the cause of the hypogonadism. Others did find that better responses were found in post-pubertal hypogonadism. Our findings are in line with others, all men in our cohort had both hCG and FSH, and all had been previously been on some form of testosterone replacement therapy. All our men administered their alternate day injections; none reported any problems with this or any complications or side effects.
Our success rates compare well with other published data. There are very little published data beyond our own results with which to counsel couples considering treatment in a nonspecialist unit providing gonadotropin therapy. We suggest that there is a need to collect these data nationally to inform couples about the likely success of treatment. Costs per man treated to achieve spermatogenesis are low and well within WHO guideline limits for cost-effective treatments [11]. Median treatment duration whether successful or not was of the order of 18–24 months (434 and 455 days, respectively). This is clearly a long time to maintain compliance over, but our experience is that patients seem very dedicated to and compliant with the treatment. Despite this, many clinics (in a UK-based survey) view cost as a major barrier to initiation or continuation of treatment [12].
Purpose We compared our clinical experience to international standards, assessed by response to treatment and pregnancy rates to ensure our results were comparable.
Methods Men presenting with azoospermia related to hypogonadism were recruited into a treatment program that was managed by one person over 8 years in a secondary care facility. Treatment followed published management plans using urinary gonadotropins. Data were collected on success rates in spermatogenesis, as well as variables that might predict success, and costs. Statistical analysis used non-parametric methods.
Results Of 16 men with HH, 14 achieved spermatogenesis, and 9 had sperm cryopreserved. Of those 14, 6 were successful in achieving a pregnancy with their partner from assisted conception (including ICSI) and one after natural conception. Factors identified to identify men likely to be successful in treatment were whether the testicular volume was larger at the onset of gonadotropins (median 10 mL) with a trend towards greater success if the cause developed after puberty. Mean treatment costs per man treated amounted to GP£4379/UD$5377 (figures for September 2020).
Summary Success rates from this treatment should exceed 70% in most clinical settings. The likelihood of success improves when testicular volume exceeded 10 mL at the initiation of treatment and a trend exists whereby success is more likely whereby when hypogonadism developed after puberty. Treatment costs are at a level likely to benefit the quality of life, supporting the delivery of this treatment, and where necessary and possible, funding is in line with other fertility treatments. This treatment should be available much more widely as a management option for men with hypogonadism, allowing them to father a biological child, rather than using donor sperm.
Introduction
Disorders of sperm function and production are found in 36% of the infertile population [1], but related endocrine causes are rare. One large cohort study of men with sperm disorders found that only 18 of 1035 men (1.7%) had a “clinically significant” endocrine disorder [2]. Severe forms of endocrine-related sperm production disorders include those dysfunctions of the hypothalamic-pituitary axis which result in hypogonadotropic hypogonadism, either are related to anosmia (Kallmann syndrome) or are idiopathic (IHH). Hypogonadotropic hypogonadism is rare, occurring in fewer than one man in 500 [1]. In the paper referred to above, hypogonadotropic hypogonadism was the cause of the man’s infertility in only 2 of the 1035 (0.3%) [2]. This condition is therefore rare but amenable to long-established, effective treatment, by regular gonadotropin injections, usually self-administered [3]. But what is the cost of this treatment and … do some clinics shy away from treating men with IHH because of cost?
Response to treatment is related to the underlying cause of HH: men with postpubertal acquired HH have the best response to treatment and achieve higher pregnancy rates [4]. Combined (hCG and FSH) gonadotropin use treats both hypothalamic and primary pituitary causes of HH and may require quite prolonged stimulation, up to 24 months [5]. Other predictors of a positive response to treatment include larger baseline testicular size and absence of undescended testes. Negative predictors for response to treatment include smaller testicular volume and pubertal status [6].
Our clinical work is undertaken in a secondary care hospital, not in a specialist unit, and we wanted firstly to ensure our results were comparable with national and international standards, secondly to consider if there were any predictive factors evident between the successful and unsuccessful groups and finally to estimate the cost for the treatment. Published literature suggests that 60–75% of men should have sperm (> 1.5 × 106 sperm/mL) on completion of treatment—that is, after 6 months [5, 7]. The aim of treatment in our unit is to induce sufficient numbers of sperm so as to allow sperm to be stored and used at a later date, with the expectation that would be using in vitro fertilization associated with intracytoplasmic sperm injection.
Methods
We used a treatment approach in line with published effective protocols [5, 7]. These involve hCG injections (2000 IU IM) three times a week followed by serum testosterone measured at 4 weeks. Once serum testosterone exceeded 10 nmol/L (288 ng/dL) in line with other published studies [5, 7], the follicle-stimulating hormone was added (FSH 75 IU SC) three times a week. Different proprietary formulations of hCG and FSH injections were used throughout the span of the review—generally the least expensive that the hospital pharmacy could purchase, and generally a urinary derived gonadotropin product. The seminal fluid analysis was performed 4 months after commencing FSH treatment. If there were no sperm present, the dose of FSH was increased to 150 IU SC three times a week, and a further sample assessed 4 months later. Once sperm were observed in the sample, arrangements were made for sperm to be freeze stored. If sperm were not seen on the second sample, gonadotropin therapy was discontinued.
Discussion
The data in this paper are small and might be dismissed as a result, this being seen as a weakness. However, they are data from one clinical service in a teaching hospital, not from a specialist fertility center, and not from a research program, offering gonadotropin therapy for spermatogenesis for over 15 years. This review of the outcomes from our clinical service affirms the importance and effectiveness of spermatogenesis as a treatment and supports the provision of gonadotropin induction of spermatogenesis in a secondary care setting and shows that these patients do not have to be managed in a tertiary fertility unit.
Spermatogenesis was achieved in 14 of 16 men (88%); this compares well with published data in which rates of 60– 75% were achieved with gonadotropin therapy [5, 7]. Larger initial testicular volumes were more likely to lead to success at spermatogenesis, as others have found [6]. We found a trend whereby successful treatment was more likely in men with post-pubertal hypogonadism causes, while others found no difference in the cause of the hypogonadism. Others did find that better responses were found in post-pubertal hypogonadism. Our findings are in line with others, all men in our cohort had both hCG and FSH, and all had been previously been on some form of testosterone replacement therapy. All our men administered their alternate day injections; none reported any problems with this or any complications or side effects.
Our success rates compare well with other published data. There are very little published data beyond our own results with which to counsel couples considering treatment in a nonspecialist unit providing gonadotropin therapy. We suggest that there is a need to collect these data nationally to inform couples about the likely success of treatment. Costs per man treated to achieve spermatogenesis are low and well within WHO guideline limits for cost-effective treatments [11]. Median treatment duration whether successful or not was of the order of 18–24 months (434 and 455 days, respectively). This is clearly a long time to maintain compliance over, but our experience is that patients seem very dedicated to and compliant with the treatment. Despite this, many clinics (in a UK-based survey) view cost as a major barrier to initiation or continuation of treatment [12].
