Luteinizing hormone supplementation in women with hypogonadotropic hypogonadism seeking fertility care: Insights from a narrative review.
Ontology highlight
ABSTRACT:
SUBMITTER: Di Segni N
PROVIDER: S-EPMC9377693 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Luteinizing hormone supplementation in women with hypogonadotropic hypogonadism seeking fertility care: Insights from a narrative review.
Di Segni Noemi N Busnelli Andrea A Secchi Matteo M Cirillo Federico F Levi-Setti Paolo Emanuele PE
Frontiers in endocrinology 20220801
The management of infertile women affected by hypogonadotropic hypogonadism (HH) or conditions mimicking it is particularly challenging. In the present narrative review, we aimed to synthesize the available evidence on the benefit (if any) of exogenous luteinizing hormone (LH) supplementation in this group of patients. Available data support LH supplementation in women with organic or functional HH. On the contrary, the benefit of exogenous LH on reproductive outcomes both in advanced maternal a ...[more]
Similar Datasets
Project description:ObjectiveLittle is known about how women with isolated GnRH deficiency cope with their condition. This study aimed to examine the health and informational needs of women with congenital hypogonadotropic hypogonadism (CHH) and evaluate if their experiences differ from women with more common forms of infertility.DesignCross-sectional, multiple methods study using web-based data collection to reach dispersed rare disease patients.MethodsA community-based participatory research framework was employed to develop an online survey and collect quantitative and qualitative data. Adult women diagnosed with CHH who had received at least one year of hormonal treatment completed the Morisky Medication Adherence Scale, Revised Illness Perception Questionnaire and Zung Self-Rating Depression Scale. Information on health care experiences, treatment outcomes and patient-reported challenges were also collected.ResultsWomen (n = 55) were often diagnosed late (20.7 ± 7.4, range: 10-48 years) and 16/20 patients receiving fertility treatment conceived. Poor adherence was frequently observed (34/55) while more than half (27/49) reported a gap in treatment exceeding a year. Low adherence correlated with depressive symptoms (r = 0.3, P > 0.05). Negative illness perceptions were pervasive and 30/55 exhibited some depressive symptoms - significantly greater than women with common female factor infertility (P < 0.01). Symptoms were underappreciated by providers as only 15 of 55 patients had discussions about psychological services. Women identified isolation, need for information and finding expert care as challenges to living with CHH.ConclusionsDespite being a treatable form of female infertility, the presumable availability of treatment does not necessarily ensure adequate quality of life for women with isolated GnRH deficiency.
| S-EPMC5551425 | biostudies-literature
Project description:Human sexual and reproductive development is regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which is primarily controlled by the gonadotropin-releasing hormone (GnRH) acting on its receptor (GnRHR). Dysregulation of the axis leads to conditions such as congenital hypogonadotropic hypogonadism (CHH) and delayed puberty. The pathophysiology of GnRHR makes it a potential target for treatments in several reproductive diseases and in congenital adrenal hyperplasia. GnRHR belongs to the G protein-coupled receptor family and its GnRH ligand, when bound, activates several complex and tissue-specific signaling pathways. In the pituitary gonadotrope cells, it triggers the G protein subunit dissociation and initiates a cascade of events that lead to the production and secretion of the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) accompanied with the phospholipase C, inositol phosphate production, and protein kinase C activation. Pharmacologically, GnRHR can be modulated by synthetic analogues. Such analogues include the agonists, antagonists, and the pharmacoperones. The agonists stimulate the gonadotropin release and lead to receptor desensitization with prolonged use while the antagonists directly block the GnRHR and rapidly reduce the sex hormone production. Pharmacoperones include the most recent GnRHR therapeutic approaches that directly correct the misfolded GnRHRs, which are caused by genetic mutations and hold serious promise for CHH treatment. Understanding of the GnRHR's genomic and protein structure is crucial for the most appropriate assessing of the mutation impact. Such mutations in the GNRHR are linked to normosmic hypogonadotropic hypogonadism and lead to various clinical symptoms, including delayed puberty, infertility, and impaired sexual development. These mutations vary regarding their mode of inheritance and can be found in the homozygous, compound heterozygous, or in the digenic state. GnRHR expression extends beyond the pituitary gland, and is found in reproductive tissues such as ovaries, uterus, and prostate and non-reproductive tissues such as heart, muscles, liver and melanoma cells. This comprehensive review explores GnRHR's multifaceted role in human reproduction and its clinical implications for reproductive disorders.
| S-EPMC10650312 | biostudies-literature
Project description:Context and objectiveThe optimal strategy for inducing fertility in men with congenital hypogonadotropic hypogonadism (CHH) is equivocal. Albeit a biologically plausible approach, pretreatment with recombinant FSH (rFSH) before GnRH/human chorionic gonadotropin administration has not been sufficiently assessed. The objective of the study was to test this method.Design and settingThis was a randomized, open-label treatment protocol at an academic medical center.Patients and interventionsGnRH-deficient men (CHH) with prepubertal testes (<4 mL), no cryptorchidism, and no prior gonadotropin therapy were randomly assigned to either 24 months of pulsatile GnRH therapy alone (inducing endogenous LH and FSH release) or 4 months of rFSH pretreatment followed by 24 months of GnRH therapy. Patients underwent serial testicular biopsies, ultrasound assessments of testicular volume, serum hormone measurements, and seminal fluid analyses.ResultsrFSH treatment increased inhibin B levels into the normal range (from 29 ± 9 to 107 ± 41 pg/mL, P < .05) and doubled testicular volume (from 1.1 ± 0.2 to 2.2 ± 0.3 mL, P < .005). Histological analysis showed proliferation of both Sertoli cells (SCs) and spermatogonia, a decreased SC to germ cell ratio (from 0.74 to 0.35), and SC cytoskeletal rearrangements. With pulsatile GnRH, the groups had similar hormonal responses and exhibited significant testicular growth. All men receiving rFSH pretreatment developed sperm in their ejaculate (7 of 7 vs 4 of 6 in the GnRH-only group) and showed trends toward higher maximal sperm counts.ConclusionsrFSH pretreatment followed by GnRH is successful in inducing testicular growth and fertility in men with CHH with prepubertal testes. rFSH not only appears to maximize the SC population but also induces morphologic changes, suggesting broader developmental roles.
| S-EPMC3816270 | biostudies-literature
Project description:A multicenter, open-label, randomized, controlled superiority trial with 18 months of follow-up was conducted to investigate whether oral zinc supplementation could further promote spermatogenesis in males with isolated hypogonadotropic hypogonadism (IHH) receiving sequential purified urinary follicular-stimulating hormone/human chorionic gonadotropin (uFSH/hCG) replacement. Sixty-seven Chinese male IHH patients were recruited from the Departments of Endocrinology in eight tertiary hospitals and randomly allocated into the sequential uFSH/hCG group (Group A, n = 34) or the sequential uFSH plus zinc supplementation group (Group B, n = 33). In Group A, patients received sequential uFSH (75 U, three times a week every other 3 months) and hCG (2000 U, twice a week) treatments. In Group B, patients received oral zinc supplementation (40 mg day-1 ) in addition to the sequential uFSH/hCG treatment given to patients in Group A. The primary outcome was the proportion of patients with a sperm concentration ≥1.0 × 106 ml-1 during the 18 months. The comparison of efficacy between Groups A and B was analyzed. Nineteen of 34 (55.9%) patients receiving sequential uFSH/hCG and 20 of 33 (60.6%) patients receiving sequential uFSH/hCG plus zinc supplementation achieved sperm concentrations ≥1.0 × 106 ml-1 by intention to treat analyses. No differences between Group A and Group B were observed as far as the efficacy of inducing spermatogenesis (P = 0.69). We concluded that the sequential uFSH/hCG plus zinc supplementation regimen had a similar efficacy to the sequential uFSH/hCG treatment alone. The additional improvement of 40 mg day-1 oral zinc supplementation on spermatogenesis and masculinization in male IHH patients is very subtle.
| S-EPMC5427781 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to evaluate the reproductive outcome of patients with hypogonadotropic hypogonadism (HH) receiving in vitro fertilization and embryo transfer (IVF-ET).MethodsThe reproductive outcome of 81 HH patients and 112 controls who underwent oocyte retrieval was evaluated retrospectively in the Center for Reproductive Medicine of Peking University Third Hospital from 2010 to 2019.ResultsThe basic levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), androstenedione (A) and prolactin (PRL) were significantly lower in the HH group than the control group. Although the HH patients required a significantly longer stimulation and higher gonadotropin (Gn) doses than the control patients, the total number of oocytes retrieved, fertilized embryos, two pronuclear (2PN) embryos, transferable embryos, fertilization and 2PN rates were comparable between the two groups. Although the live birth rate (LBR) of the first fresh cycle was higher in the control group than the HH group, there was no statistical significance. Then we further divided HH patients into two subgroups according to the etiology. Forty-one cases were termed as congenital HH (CHH), while the other 40 cases were termed as acquired HH (AHH), the latter includes functional hypothalamic amenorrhea (FHA) and pituitary HH (PHH). Our results showed that there were no significant differences in basic clinical characteristics and IVF parameters between the two groups. In the HH group, a total of 119 oocyte retrieval cycles were carried out and they responded adequately to ovulation induction. Urinary human menopausal gonadotropin (HMG) was used alone in 90 cycles while combination of HMG and recombinant human follicle stimulating hormone (rFSH) in the other 29 cycles. There were no significant differences in IVF-related parameters between the two groups. The conservative cumulative live birth rates (CLBRs) after the first, the second and ≥third cycles were 43.21%, 58.02% and 60.49%, respectively, while the corresponding optimal CLBRs were 43.21%, 68.45% and 74.19%. The preterm birth (PTB) rates of singletons and twin pregnancy in HH patients were 8.33% (3/36) and 30.77% (4/13), respectively.ConclusionIVF-ET is an effective treatment for HH patients with infertility and patients can get satisfactory pregnancy outcomes.
| S-EPMC9208655 | biostudies-literature
Project description:Male congenital hypogonadotropic hypogonadism (CHH) is a heterogenous group of genetic disorders that cause impairment in the production or action of gonadotropin releasing hormone (GnRH). These defects result in dysfunction of the hypothalamic-pituitary-gonadal hormone axis, leading to low testosterone levels and impaired fertility. Genetic testing techniques have expanded our knowledge of the underlying mechanisms contributing to CHH including over 30 genes to date implicated in the development of CHH. In some cases, non-reproductive signs or symptoms can give clues as to the putative genetic etiology, but many cases remain undiagnosed with less than 50% identified with a specific gene defect. This leads to many patients labelled as "idiopathic hypogonadotropic hypogonadism". Medical and family history as well as physical exam and laboratory features can aid in the identification of hypogonadotropic hypogonadism (HH) that is associated with specific medical syndromes or associated with other pituitary hormonal deficiencies. Genetic testing strategies are moving away from the classic practice of testing for only a few of the most commonly affected genes and instead utilizing next generation sequencing techniques that allow testing of numerous potential gene targets simultaneously. Treatment of CHH is dependent on the individual's desire to preserve fertility and commonly include human chorionic gonadotropin (hCG) and recombinant follicle stimulating hormone (rFSH) to stimulate testosterone production and spermatogenesis. In situations where fertility is not desired, testosterone replacement therapies are widely offered in order to maintain virilization and sexual function.
| S-EPMC8039576 | biostudies-literature
Project description: Not available
| S-EPMC5943644 | biostudies-literature
Project description:Study questionWhat is the contribution of genetic defects in Portuguese patients with congenital hypogonadotropic hypogonadism (CHH)?Summary answerApproximately one-third of patients with CHH were found to have a genetic cause for their disorder, with causal pathogenic and likely pathogenic germline variants distributed among 10 different genes; cases of oligogenic inheritance were also included.What is known alreadyCHH is a rare and genetically heterogeneous disorder characterized by deficient production, secretion, or action of GnRH, LH, and FSH, resulting in delayed or absent puberty, and infertility.Study design size durationGenetic screening was performed on a cohort of 81 Portuguese patients with CHH (36 with Kallmann syndrome and 45 with normosmic hypogonadotropic hypogonadism) and 263 unaffected controls.Participants/materials setting methodsThe genetic analysis was performed by whole-exome sequencing followed by the analysis of a virtual panel of 169 CHH-associated genes. The main outcome measures were non-synonymous rare sequence variants (population allele frequency <0.01) classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS).Main results and the role of chanceA genetic cause was identified in 29.6% of patients. Causal pathogenic and likely pathogenic variants were distributed among 10 of the analysed genes. The most frequently implicated genes were GNRHR, FGFR1, ANOS1, and CHD7. Oligogenicity for pathogenic and likely pathogenic variants was observed in 6.2% of patients. VUS and oligogenicity for VUS variants were observed in 85.2% and 54.3% of patients, respectively, but were not significantly different from that observed in controls.Large scale dataN/A.Limitations reasons for cautionThe identification of a large number of VUS presents challenges in interpretation and these may require reclassification as more evidence becomes available. Non-coding and copy number variants were not studied. Functional studies of the variants were not undertaken.Wider implications of the findingsThis study highlights the genetic heterogeneity of CHH and identified several novel variants that expand the mutational spectrum of the disorder. A significant proportion of patients remained without a genetic diagnosis, suggesting the involvement of additional genetic, epigenetic, or environmental factors. The high frequency of VUS underscores the importance of cautious variant interpretation. These findings contribute to the understanding of the genetic architecture of CHH and emphasize the need for further studies to elucidate the underlying mechanisms and identify additional causes of CHH.Study funding/competing interestsThis research was funded by the Portuguese Foundation for Science and Technology (grant numbers PTDC/SAU-GMG/098419/2008, UIDB/00709/2020, CEECINST/00016/2021/CP2828/CT0002, and 2020.04924.BD) and by Sidra Medicine-a member of the Qatar Foundation (grant number SDR400038). The authors declare no competing interests.
| S-EPMC11415827 | biostudies-literature
Project description:Hereditary hemochromatosis is a genetic disease that progresses silently. This disease is often diagnosed late when complications appear. Hypogonadotropic hypogonadism (HH) is one of the classical complications of hemochromatosis. Its frequency is declining probably because of earlier diagnosis and better informed physicians. Certain symptoms linked to HH can have an impact on a patient's sexuality, such as decreased libido, erectile dysfunction, and impairment of ejaculation, as well as on his reproductive capacities. This review is based on an online search in English, French and German language publications found in PubMed/Medline, up to 23 September 2016 using the following key word: Male infertility, Hypogonadotropic Hypogonadism, Hereditary Hemochromatosis. Thirty-four papers met these inclusion criteria. This review describes the impact of iron overload on male fertility, resulting in hypogonadotropic hypogonadism and proposes treatment modalities.
| S-EPMC5501943 | biostudies-other
Project description:IntroductionThe optimal dosage of recombinant human luteinizing hormone (r-hLH) and its impact on endometrial thickness (EMT) when administered alongside recombinant human follicle-stimulating hormone (r-hFSH) during controlled ovarian stimulation (COS) for in vitro fertilization/intracytoplasmic sperm injection and embryo transfer are uncertain, which formed the aims of this systematic review and meta-analysis.MethodA search was performed in PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, and Wanfang from its inception to 10 July 2023. Twenty-seven Randomized controlled trials comparing r-hFSH/r-hLH co-treatment with r-hFSH alone during in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) were included. Pooled odds ratios (OR) for dichotomous data and mean differences (MD) for continuous data, with their respective 95% confidence intervals (CI), were generated. Meta-analysis employed fixed-effect or random-effect models based on heterogeneity, using Q-test and I2-index calculations. The main outcomes included EMT on trigger day, clinical pregnancy rate (CPR) and live birth rate (LBR).Resultsr-hFSH/r-hLH significantly increased EMT on trigger day (MD = 0.27; 95% CI, 0.11-0.42; I2 = 13%), but reduced oocyte number (MD = -0.60; 95% CI, -1.07 to -0.14; I2 = 72%) and high-quality embryos (MD = -0.76; 95% CI, -1.41 to -0.10; I2 = 94%) than r-hFSH alone, more pronounced with the gonadotrophin-releasing hormone agonist long protocol. A subgroup analysis showed r-hLH at 75 IU/day increased CPR (OR = 1.23; 95% CI, 1.02-1.49; I2 = 16%) and EMT on trigger day (MD = 0.40; 95% CI, 0.19-0.61; I2 = 0%). Participants ≥35 years of age exhibited decreased retrieved oocytes (MD = -1.26; 95% CI, -1.78 to -0.74; I2 = 29%), but an increase in EMT on trigger day (MD = 0.26; 95% CI, 0.11-0.42; I2 = 29%).Conclusionr-hFSH/r-hLH during COS significantly improved EMT compared to r-hFSH alone. An r-hLH dose of 75 IU/day may be considered for optimal pregnancy outcomes, which still require further clinical studies to support this dosing regime.Systematic review registration[www.crd.york.ac.uk/PROSPERO], identifier [CRD42023454584].
| S-EPMC11317380 | biostudies-literature