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JBRA Assisted Reproduction Jun 2024Non-obstructive azoospermia (NOA) is the most severe form of male factor infertility. It results form from either primary or secondary testicular failure. Here, we...
Two livebirths achieved in cases of hypergonadotropic hypogonadism nonobstructive azoospermia, treated with GnRH agonist and gonadotrophins: a case series and review of the literature.
Non-obstructive azoospermia (NOA) is the most severe form of male factor infertility. It results form from either primary or secondary testicular failure. Here, we report cases of two patients with NOA due to maturation arrest and increased serum FSH, treated with GnRH agonist and gonadotrophins. The two NOA patients underwent a pharmacological treatment consisting of pituitary desensibilization using a GnRH agonist and testicular stimulation using menotropin. Testicular stimulation started one month after the beginning of GnRH agonist treatment. The female partner underwent controlled ovarian stimulation (COS) followed by intracytoplasmic sperm injection (ICSI). On the third day of the cycle, menotropin daily doses was administered. When at least one follicle ≥14 mm was visualized, pituitary blockage was performed using GnRH antagonist ganirelix. When three or more follicles attained a mean diameter of ≥17 mm, triptorelin acetate was administered to trigger final follicular maturation. Oocyte retrieval was performed 35 hours later. After treatment, male partner blood levels of the FSH, LH, decreased and total testosterone were increased. Spermatozoa was observed after semen collection in both cases. After COS, oocytes were retrieved and ICSI was performed. Embryos were biopsied for preimplantation genetic testing (PGT) and those considered euploidy were transferred resulting in positive implantation, ongoing pregnancy, and livebirth on both cases. In this report we present a successful strategy for hypergonadotropic hypogonadism AOA men, as an alternative approach to the surgical testicular sperm recovery. Nevertheless, prospective randomized trials are needed to confirm our findings.
PubMed: 38875134
DOI: 10.5935/1518-0557.20240039 -
The Medical Journal of Malaysia May 2024Optimising controlled ovarian stimulation (COS) procedures for in vitro fertilisation (IVF) requires an assessment of the patients' medical history, ovarian reserve,...
INTRODUCTION
Optimising controlled ovarian stimulation (COS) procedures for in vitro fertilisation (IVF) requires an assessment of the patients' medical history, ovarian reserve, prognostic factors and resources to personalise the treatment plan. Treatment personalisation in IVF is increasingly recognised as being vital in providing a balance of efficacy and safety for patients undergoing the COS procedure. In this study, we aimed to assess the efficacy of an ovarian stimulation protocol employing a personalised dosing algorithm for a novel recombinant FSH (rFSH) derived from a human cell-line - follitropin delta, in a mixed gonadotrophin regimen with human menotrophin (HP-HMG). The main outcome of interest in this study is clinical pregnancy rate (CPR) per embryo transfer cycle.
MATERIALS AND METHODS
In this single-centre, retrospective, non-interventional study of 20 infertility patients, each individual was provided with a personalised COS regimen based on her ovarian reserve biomarker-serum anti- Mullerian hormone (AMH) and body weight, in a gonadotrophin-receptor hormone (GnRH) antagonist protocol. Personalised dosing of follitropin delta was coadministered with 75 IU of HP-hMG during the COS duration until the final oocyte maturation trigger injection. Ovarian response, pregnancy and safety outcomes resulting from this procedure were assessed and reported here.
RESULTS
Following a mean COS duration of 11 days and 50% of patients who underwent frozen embryo transfers, the CPR per started cycle was 70%. The observed CPR from this study was higher than that reported in the follitropin delta Phase 3 studies using rFSH monotherapy stimulation, and additionally showed no incidents of cycle cancellations and no iatrogenic safety risks such as ovarian hyperstimulation syndrome.
CONCLUSION
The present study provides a first glimpse into the favourable benefit: risk profile of a mixed protocol regimen using follitropin delta combined with HP-hMG in a cohort of Asian patients in Malaysia.
Topics: Humans; Female; Ovulation Induction; Retrospective Studies; Follicle Stimulating Hormone, Human; Pregnancy; Adult; Recombinant Proteins; Menotropins; Pregnancy Rate; Treatment Outcome; Fertilization in Vitro
PubMed: 38817059
DOI: No ID Found -
Archives of Endocrinology and Metabolism May 2024Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic...
Pulsatile gonadotropin releasing hormone therapy for spermatogenesis in congenital hypogonadotropic hypogonadism patients who had poor response to combined gonadotropin therapy.
OBJECTIVE
Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy.
MATERIALS AND METHODS
Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis.
RESULTS
A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/ HMG therapy (P < 0.05).
CONCLUSION
For CHH patients with prior poor response to one year of HCG/ HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis.
Topics: Humans; Male; Spermatogenesis; Gonadotropin-Releasing Hormone; Hypogonadism; Adult; Testosterone; Young Adult; Treatment Outcome; Chorionic Gonadotropin; Menotropins; Testis; Drug Therapy, Combination; Pulse Therapy, Drug; Adolescent
PubMed: 38739523
DOI: 10.20945/2359-4292-2023-0101 -
Reproductive Biology and Endocrinology... Jan 2024The maximum daily dose of follitropin delta for ovarian stimulation in the first in vitro fertilization cycle is 12 μg (180 IU), according to the algorithm...
BACKGROUND
The maximum daily dose of follitropin delta for ovarian stimulation in the first in vitro fertilization cycle is 12 μg (180 IU), according to the algorithm developed by the manufacturer, and based on patient's ovarian reserve and weight. This study aimed to assess whether 150 IU of menotropin combined with follitropin delta improves the response to stimulation in women with serum antimullerian hormone levels less than 2.1 ng/mL.
METHODS
This study involved a prospective intervention group of 44 women who received 12 μg of follitropin delta combined with 150 IU of menotropin from the beginning of stimulation and a retrospective control group of 297 women who received 12 μg of follitropin delta alone during the phase 3 study of this drug. The inclusion and exclusion criteria and other treatment and follow-up protocols in the two groups were similar. The pituitary suppression was achieved by administering a gonadotropin-releasing hormone (GnRH) antagonist. Ovulation triggering with human chorionic gonadotropin or GnRH agonist and the option of transferring fresh embryos or using freeze-all strategy were made according to the risk of developing ovarian hyperstimulation syndrome.
RESULTS
Women who received follitropin delta combined with menotropin had higher estradiol levels on trigger day (2150 pg/mL vs. 1373 pg/mL, p < 0.001), more blastocysts (3.1 vs. 2.4, p = 0.003) and more top-quality blastocysts (1.8 vs. 1.3, p = 0.017). No difference was observed in pregnancy, implantation, miscarriage, and live birth rates after the first embryo transfer. The incidence of ovarian hyperstimulation syndrome did not differ between the groups. However, preventive measures for the syndrome were more frequent in the group using both drugs than in the control group (13.6% vs. 0.6%, p < 0.001).
CONCLUSIONS
In women with serum antimullerian hormone levels less than 2.1 ng/mL, the administration of 150 IU of menotropin combined with 12 μg of follitropin delta improved the ovarian response, making it a valid therapeutic option in situations where ovulation triggering with a GnRH agonist and freeze-all embryos strategy can be used routinely.
TRIAL REGISTRATION
U1111-1247-3260 (Brazilian Register of Clinical Trials, available at https://ensaiosclinicos.gov.br/rg/RBR-2kmyfm ).
Topics: Pregnancy; Humans; Female; Ovarian Hyperstimulation Syndrome; Menotropins; Prospective Studies; Retrospective Studies; Anti-Mullerian Hormone; Pregnancy Rate; Fertilization in Vitro; Ovulation Induction; Gonadotropin-Releasing Hormone
PubMed: 38166856
DOI: 10.1186/s12958-023-01172-9 -
BMC Pregnancy and Childbirth Jul 2023GnRHa and hCG are both used for oocyte maturation and ovulation triggering. However, GnRHa have a shorter half-life than hCG, which leads to luteal phase deficiency....
BACKGROUND
GnRHa and hCG are both used for oocyte maturation and ovulation triggering. However, GnRHa have a shorter half-life than hCG, which leads to luteal phase deficiency. Letrozole (LE) has been found to improve the luteal function. Thus, the choice of triggering strategy can be different in intrauterine insemination (IUI) cycles using LE and human menopausal gonadotropin (HMG). The aim of this study was to compare the pregnancy and neonatal outcomes of patients triggered with GnRHa versus hCG versus dual trigger in LE-IUI cycles.
METHODS
This retrospective cohort study included 6,075 LE-HMG IUI cycles between January 2010 and May 2021 at a tertiary-care academic medical center in China. All cycles were divided into three groups according to different trigger strategies as hCG trigger group, GnRHa trigger group and dual trigger group. The primary outcome was clinical pregnancy rate. Logistic regression analysis was performed to explore other risk factors for clinical pregnancy rate.
RESULTS
No significant difference was observed in clinical pregnancy rate between hCG, GnRHa and dual trigger cycles in LE-HMG IUI cycles (P = 0.964). The miscarriage rate was significantly lower in the GnRHa trigger group, and higher in the dual trigger group, compared with the hCG group (P = 0.045). Logistic analysis confirmed that triggering strategy was associated with miscarriage (aOR:0.427, 95%CI: 0.183-0.996, P = 0.049; aOR:0.298, 95%CI: 0.128-0.693, P = 0.005). No significant differences were observed regarding neonatal outcomes between the three groups.
CONCLUSIONS
Our findings suggested that both GnRHa and dual trigger can be used to trigger ovulation in LE-HMG IUI cycles, but dual trigger must be used with caution.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Letrozole; Menotropins; Abortion, Spontaneous; Retrospective Studies; Ovulation Induction; Chorionic Gonadotropin; Fertilization in Vitro; Pregnancy Rate; Insemination, Artificial; Gonadotropin-Releasing Hormone
PubMed: 37442967
DOI: 10.1186/s12884-023-05835-8 -
Gynecologic and Obstetric Investigation 2023The aim of the study was to evaluate dosing of recombinant human luteinizing hormone (r-hLH) or human menopausal gonadotrophin (hMG)-derived medications with LH activity...
Dosing Characteristics of Recombinant Human Luteinizing Hormone or Human Menopausal Gonadotrophin-Derived LH Activity in Patients Undergoing Ovarian Stimulation: A German Fertility Database Study.
OBJECTIVES
The aim of the study was to evaluate dosing of recombinant human luteinizing hormone (r-hLH) or human menopausal gonadotrophin (hMG)-derived medications with LH activity in ovarian stimulation (OS) cycles for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).
DESIGN
A non-interventional study was performed to analyse data from the German RecDate database (January 2007-December 2011).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Starting/total r-hLH/hMG dose, OS duration/cycle number, r-hLH/hMG initiation day (first day of administration), and population/cycle characteristics were assessed in women (≥18 years) undergoing OS for IVF/ICSI using r-hLH or hMG-derived medications (excluding corifollitropin alfa, clomiphene citrate, letrozole, mini/micro-dose human chorionic gonadotrophin, and urofollitropin alone). Data were summarized descriptively.
RESULTS
67,858 identified cycles utilized medications containing r-hLH (10,749), hMG (56,432), or both (677). Mean (standard deviation) OS duration with r-hLH and hMG was 10.1 (4.43) and 9.8 (6.16) days, respectively. Median (25th-75th percentile) r-hLH starting dose (75.0 [75.0-150.0] IU) was consistent across patients regardless of age, infertility diagnosis, or gonadotrophin-releasing hormone (GnRH) protocol. Median (25th-75th percentile) hMG-derived LH activity starting dose was 225.0 (150.0-300.0) IU, regardless of GnRH protocol, but was lower in women aged <35 years and those with ovulation disorders/polycystic ovary syndrome. Median (25th-75th percentile) total dose for r-hLH (750.0 [337.5-1,125.0] IU) and hMG-derived LH activity (1,575.0 [750.0-2,625.0] IU) varied according to patients' age, infertility diagnosis, cycle number, and r-hLH/hMG initiation day. GnRH antagonist use resulted in a numerically higher median total hMG-derived LH activity dose than GnRH agonist use.
LIMITATIONS
The data used in this study were taken from electronic medical records relating to a specific timeframe (2007-2011) and therefore may not accurately reflect current clinical practice; however, it is likely that the differences between the two compounds would be maintained. Additionally, secondary data sources may suffer from uniformity and quality issues.
CONCLUSIONS
The standard of care for OS cycles is described with respect to IVF/ICSI treatment including an LH component in Germany during the specified timeframe.
Topics: Humans; Female; Male; Semen; Luteinizing Hormone; Menotropins; Ovulation Induction; Gonadotropin-Releasing Hormone; Fertilization in Vitro; Infertility; Menopause; Fertility
PubMed: 37369184
DOI: 10.1159/000530360 -
Best Practice & Research. Clinical... Jun 2023This comparative non-interventional study using data from the French National Health Database (Système National des Données de Santé) investigated real-world... (Comparative Study)
Comparative Study Observational Study
Comparative effectiveness of gonadotropins used for ovarian stimulation during assisted reproductive technologies (ART) in France: A real-world observational study from the French nationwide claims database (SNDS).
This comparative non-interventional study using data from the French National Health Database (Système National des Données de Santé) investigated real-world (cumulative) live birth outcomes following ovarian stimulation, leading to oocyte pickup with either originator recombinant human follicle-stimulating hormone (r-hFSH) products (alfa or beta), r-hFSH alfa biosimilars, or urinaries including mainly HP-hMG (menotropins), and marginally u-hFSH-HP (urofollitropin). Using data from 245,534 stimulations (153,600 women), biosimilars resulted in a 19% lower live birth (adjusted odds ratio (OR) 0.81, 95% confidence interval (CI) 0.76-0.86) and a 14% lower cumulative live birth (adjusted hazard ratio (HR) 0.86, 95% CI 0.82-0.89); and urinaries resulted in a 7% lower live birth (adjusted OR 0.93, 95% CI 0.90-0.96) and an 11% lower cumulative live birth (adjusted HR 0.89, 95% CI 0.87-0.91) versus originator r-hFSH alfa. Results were consistent across strata (age and ART strategy), sensitivity analysis using propensity score matching, and with r-hFSH alfa and beta as the reference group.
Topics: Female; Humans; Pregnancy; Biosimilar Pharmaceuticals; Follicle Stimulating Hormone, Human; Gonadotropins; Ovulation Induction; Reproductive Techniques, Assisted
PubMed: 36707343
DOI: 10.1016/j.bpobgyn.2022.102308 -
Frontiers in Endocrinology 2022To compare the effects of human menopausal gonadotropin (HMG) combined with letrozole (LE) to HMG only for ovarian stimulation on pregnancy outcome of infertile patients...
Retrospective analysis: The application of human menopausal gonadotropin combined with letrozole for IUI in patients undergoing artificial insemination by husband due to unexplained or mild male factors.
OBJECTIVE
To compare the effects of human menopausal gonadotropin (HMG) combined with letrozole (LE) to HMG only for ovarian stimulation on pregnancy outcome of infertile patients undergoing artificial insemination by husband (AIH) due to unexplained or mild male factors.
MATERIALS AND METHODS
Infertile patients with unexplained or mild male factors treated from July 2015 to December 2021 were selected as subjects. The patients were divided into two groups according to the ovarian stimulation schemes they received, namely HMG combined with LE or HMG only. We analyzed the laboratory examination results before drug treatment (baseline) and during ovarian stimulation and compared the pregnancy outcomes of the two groups using univariable analysis and multivariable logistic regression analysis.
RESULTS
In total, 526 cycles of 372 couples were included. The univariate analysis showed that the clinical pregnancy rate of the HMG combined with LE group was 24.8%, significantly higher than that of the HMG group (14.8%, P = 0.007). The live birth rate (19.9%) of the HMG combined with LE group were also significantly higher than those of the HMG group (11.2%, respectively). In multivariate logistic analysis, the age of males was negatively associated with the clinical pregnancy rate (OR 0.874, 95% CI 0.793~0.963, P=0.006) and live birth (OR0.875, 95% CI 0.783~0.977, P=0.018). Moreover, ovarian stimulation with HMG+LE was the only beneficial factor significantly associated with clinical pregnancy (OR 1.929, 95% CI 1.068~3.485, P=0.029) and live birth (OR 2.255, 95% CI 1.188~4.282, P=0.013).
CONCLUSION
Ovarian stimulation using HMG combined with LE can increase the clinical outcomes (live birth and clinical pregnancy) among infertile patients undergoing AIH due to explained or mild male factors.
Topics: Female; Humans; Pregnancy; Male; Letrozole; Menotropins; Retrospective Studies; Spouses; Insemination, Artificial; Infertility
PubMed: 36605946
DOI: 10.3389/fendo.2022.1038433 -
Journal of Assisted Reproduction and... Jan 2023An impact of different gonadotrophins selection for ovarian stimulation (OS) on oocyte competence has yet to be defined. In this study, we asked whether an association...
PURPOSE
An impact of different gonadotrophins selection for ovarian stimulation (OS) on oocyte competence has yet to be defined. In this study, we asked whether an association exists between OS protocol and euploid blastocyst rate (EBR) per metaphase-II (MII) oocytes.
METHODS
Cycles of first preimplantation genetic testing for aneuploidies conducted by women ≥ 35 years old with their own metaphase-II oocytes inseminated in the absence of severe male factor (years 2014-2018) were clustered based on whether recombinant FSH (rec-FSH) or human menopausal gonadotrophin (HMG) was used for OS, then matched for the number of fresh inseminated eggs. Four groups were outlined: rec-FSH (N = 57), rec-FSH plus rec-LH (N = 55), rec-FSH plus HMG (N = 112), and HMG-only (N = 127). Intracytoplasmic sperm injection, continuous blastocyst culture, comprehensive chromosome testing to assess full-chromosome non-mosaic aneuploidies and vitrified-warmed euploid single embryo transfers (SETs) were performed. The primary outcome was the EBR per cohort of MII oocytes. The secondary outcome was the live birth rate (LBR) per first SETs.
RESULTS
Rec-FSH protocol was shorter and characterized by lower total gonadotrophin (Gn) dose. The linear regression model adjusted for maternal age showed no association between the Gn adopted for OS and EBR per cohort of MII oocytes. Similarly, no association was reported with the LBR per first SETs, even when adjusting for blastocyst quality and day of full blastulation.
CONCLUSION
In view of enhanced personalization in OS, clinicians shall focus on different endpoints or quantitative effects related to Gn action towards follicle recruitment, development, and atresia. Here, LH and/or hCG was administered exclusively to women with expected sub/poor response; therefore, we cannot exclude that specific Gn formulations may impact patient prognosis in other populations.
Topics: Male; Female; Humans; Adult; Case-Control Studies; Maternal Age; Metaphase; Semen; Gonadotropins; Oocytes; Ovulation Induction; Menotropins; Follicle Stimulating Hormone; Aneuploidy; Fertilization in Vitro
PubMed: 36586005
DOI: 10.1007/s10815-022-02684-w -
Medicine Oct 2022Polycystic ovary syndrome (PCOS) is a main cause of anovulatory infertility in women of reproductive age. About 30% to 50% of patients with PCOS has high serum basal...
INTRODUCTION
Polycystic ovary syndrome (PCOS) is a main cause of anovulatory infertility in women of reproductive age. About 30% to 50% of patients with PCOS has high serum basal luteinizing hormone (LH) levels, and almost 5% of PCOS women with high LH have poor ovarian response (POR). We reported a case of a PCOS woman with high basal LH levels who canceled due to POR during two consecutive controlled ovarian stimulation treatments, which was considered to be related to the suppression of LH levels during downregulation. Clomiphene citrate (CC) combined with human menopausal urinary gonadotropin (HMG) mild regimen did not affect LH levels and obtained good follicular development, providing a new treatment insight for patients with PCOS combined with POR.
PATIENT CONCERNS
A 28-year-old PCOS woman with high basal LH levels, underwent IVF assisted pregnancy treatment in our hospital, whom canceled due to POR during two traditional controlled ovulation induction program. Follicular development was finally achieved with CC milder protocol.
DIAGNOSIS
This patient with the diagnosis of PCOS was undergone IVF assisted pregnancy treatment in our hospital.
INTERVENTIONS
CC protocol supports the development of follicular.
OUTCOMES
CC protocol resulted in better follicular development and high-quality embryos due to the continuous maintenance of an elevated LH levels.
CONCLUSION
PCOS women with poor ovarian response required relatively higher LH to maintain the normal development of follicles.
Topics: Pregnancy; Female; Humans; Adult; Polycystic Ovary Syndrome; Clomiphene; Luteinizing Hormone; Ovulation Induction; Fertility Agents, Female; Menotropins
PubMed: 36281179
DOI: 10.1097/MD.0000000000031323