Does hormonal therapy improve sperm retrieval rates in men with non-obstructive azoospermia: a systematic review and meta-analysis
Abstract BACKGROUND The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Associat...
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Published in | Human reproduction update Vol. 28; no. 5; pp. 609 - 628 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
25.08.2022
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Subjects | |
Online Access | Get full text |
ISSN | 1355-4786 1460-2369 1362-4946 1460-2369 |
DOI | 10.1093/humupd/dmac016 |
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Abstract | Abstract
BACKGROUND
The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40–60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates.
OBJECTIVE AND RATIONALE
The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men.
SEARCH METHODS
A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated.
OUTCOMES
A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08–3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03–3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10–4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44–6.77, P = 0.43). The literature was at moderate or severe risk of bias.
WIDER IMPLICATIONS
This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings. |
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AbstractList | The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates.BACKGROUNDThe beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates.The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men.OBJECTIVE AND RATIONALEThe primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men.A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated.SEARCH METHODSA literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated.A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias.OUTCOMESA total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias.This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings.WIDER IMPLICATIONSThis meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings. BACKGROUND: The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates. OBJECTIVE AND RATIONALE: The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men. SEARCH METHODS: A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated. OUTCOMES: A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias. WIDER IMPLICATIONS: This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings. Abstract BACKGROUND The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40–60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates. OBJECTIVE AND RATIONALE The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men. SEARCH METHODS A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated. OUTCOMES A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08–3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03–3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10–4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44–6.77, P = 0.43). The literature was at moderate or severe risk of bias. WIDER IMPLICATIONS This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings. The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates. The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men. A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated. A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias. This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings. |
Author | Tharakan, Tharu Minhas, Suks Jayasena, Channa N Giwercman, Aleksander Foran, Daniel Krausz, Csilla Corona, Giovanni Yap, Tet Salonia, Andrea Sofikitis, Nikolaos |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35526153$$D View this record in MEDLINE/PubMed |
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ContentType | Journal Article |
Copyright | The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. 2022 The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com. The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. |
Copyright_xml | – notice: The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. 2022 – notice: The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com. – notice: The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. |
CorporateAuthor | Reproductive medicine, Malmö Institutionen för translationell medicin Reproduktionsmedicin, Malmö Department of Translational Medicine Lunds universitet Profile areas and other strong research environments Lund University Strategiska forskningsområden (SFO) EpiHealth: Epidemiology for Health Faculty of Medicine Strategic research areas (SRA) Medicinska fakulteten Profilområden och andra starka forskningsmiljöer |
CorporateAuthor_xml | – name: Faculty of Medicine – name: Medicinska fakulteten – name: Strategiska forskningsområden (SFO) – name: EpiHealth: Epidemiology for Health – name: Strategic research areas (SRA) – name: Lunds universitet – name: Profilområden och andra starka forskningsmiljöer – name: Lund University – name: Reproductive medicine, Malmö – name: Department of Translational Medicine – name: Profile areas and other strong research environments – name: Reproduktionsmedicin, Malmö – name: Institutionen för translationell medicin |
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Keywords | selective oestrogen receptor modulators aromatase inhibitors non-obstructive azoospermia gonadotrophins testicular extraction sperm surgery hypergonadotropic hypogonadism |
Language | English |
License | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0 The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com. cc-by |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 Channa N. Jayasena and Suks Minhas contributed equally to this work. |
ORCID | 0000-0003-1010-7576 0000-0002-9894-2885 0000-0001-5816-0785 0000-0002-2578-8223 0000-0002-0595-7165 |
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PublicationDate | 2022-08-25 |
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publication-title: Front Endocrinol (Lausanne) doi: 10.3389/fendo.2018.00763 |
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BACKGROUND
The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either... The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins... BACKGROUND: The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal... |
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SubjectTerms | Clinical Medicine Gynaecology, Obstetrics and Reproductive Medicine Gynekologi, obstetrik och reproduktionsmedicin Klinisk medicin Medical and Health Sciences Medicin och hälsovetenskap Reviews |
Title | Does hormonal therapy improve sperm retrieval rates in men with non-obstructive azoospermia: a systematic review and meta-analysis |
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