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Fertility and Sterility Aug 2020To evaluate the efficacy and safety of highly purified human menotropin (HP-hMG) and recombinant follicle-stimulating hormone (rFSH) for controlled ovarian stimulation... (Comparative Study)
Comparative Study
Randomized, assessor-blinded trial comparing highly purified human menotropin and recombinant follicle-stimulating hormone in high responders undergoing intracytoplasmic sperm injection.
OBJECTIVE
To evaluate the efficacy and safety of highly purified human menotropin (HP-hMG) and recombinant follicle-stimulating hormone (rFSH) for controlled ovarian stimulation in a population of patients predicted to be high responders.
DESIGN
Randomized, open-label, assessor-blinded, parallel-group, noninferiority trial.
SETTING
Fertility centers.
PATIENT(S)
A total of 620 women with serum antimüllerian hormone (AMH) ≥5 ng/mL.
INTERVENTION(S)
Controlled ovarian stimulation with HP-hMG or rFSH in a GnRH antagonist assisted reproductive technology (ART) cycle. Fresh transfer of a single blastocyst was performed unless ovarian response was excessive, in which all embryos were cryopreserved. Subjects could undergo subsequent frozen blastocyst transfer within 6 months of randomization.
MAIN OUTCOME MEASURE(S)
Ongoing pregnancy rate (OPR) after fresh transfer (primary endpoint), as well as cumulative live birth, ovarian hyperstimulation syndrome (OHSS), and pregnancy loss rates.
RESULTS
OPR/cycle start after fresh transfer was 35.5% with HP-hMG and 30.7% with rFSH (difference: 4.7%, 95% CI -2.7%, 12.1%); noninferiority was established. Compared to rFSH, HP-hMG was associated with significantly lower OHSS (21.4% vs. 9.7% respectively; difference: -11.7%, 95% CI -17.3%, -6.1%) and cumulative early pregnancy loss rates (25.5% vs. 14.5% respectively; difference: -11.0%, 95% CI -18.8%, -3.14%). Despite 43 more transfers in the rFSH group, cumulative live birth rates were similar with HP-hMG and rFSH at 50.6% and 51.5% respectively (difference: -0.8%, 95% CI -8.7%, 7.1%).
CONCLUSION(S)
In high responders, HP-hMG provided comparable efficacy to rFSH with fewer adverse events, including pregnancy loss, suggesting its optimized risk/benefit profile in this population.
CLINICAL TRIAL REGISTRATION NUMBER
NCT02554279 (clinicaltrials.gov).
Topics: Abortion, Spontaneous; Adult; Anti-Mullerian Hormone; Biomarkers; Female; Fertility; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Humans; Infertility; Live Birth; Male; Menotropins; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Recombinant Proteins; Single Embryo Transfer; Sperm Injections, Intracytoplasmic; Treatment Outcome; United States; Young Adult
PubMed: 32416978
DOI: 10.1016/j.fertnstert.2020.03.029 -
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 -
Fertility and Sterility Aug 2020
Topics: Follicle Stimulating Hormone; HIV Infections; Humans; Menotropins; Sperm Injections, Intracytoplasmic; Viral Load
PubMed: 32624220
DOI: 10.1016/j.fertnstert.2020.04.019 -
BioMed Research International 2022The endometrium receptivity was impaired by controlled ovarian hyperstimulation (COH), which would then lead to fertility issues and increased abortion clinically. In...
The endometrium receptivity was impaired by controlled ovarian hyperstimulation (COH), which would then lead to fertility issues and increased abortion clinically. In the present study, to explore the effectiveness of Tiaojing Zhuyun Formula (TJZYF) in improving endometrial receptivity of COH rats and the possible active ingredients and mechanisms, an approach of network pharmacology was performed and a COH animal model was established. As analyzed, stigmasterol and quercetin may be the active ingredients of TJZYF on improving endometrial receptivity and positive regulation of ion transport, the cytokine-mediated signaling pathway, and endocrine process, and vascular endothelial growth factor receptor signaling pathway may be involved. Eighty female rats were divided into four groups randomly: control, model, TJZYF, and TJZYF+si-VEGFA. COH rat models were constructed by injecting with human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG). We found that both endometrial thickness and number of embryo implantations in model were substantially reduced vs. control. The gene and protein expressions of VEGF, PI3K, and p-Akt in the uterus were significantly reduced. TJZYF could increase the endometrial thickness and number of embryo implantations and enhance the expressions of VEGF, PI3K, and p-Akt in the uterus. In the TJZYF+si-VEGFA group, the effect of TJZYF was impaired. Generally, TJZYF could improve the endometrium receptivity and facilitate embryo implantation of COH rats by upregulating VEGF and enhancing the PI3K/Akt signaling pathway.
Topics: Animals; Female; Pregnancy; Rats; Chorionic Gonadotropin; Cytokines; Embryo Implantation; Endometrium; Menotropins; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Quercetin; Receptors, Vascular Endothelial Growth Factor; Signal Transduction; Stigmasterol; Vascular Endothelial Growth Factor A
PubMed: 36193314
DOI: 10.1155/2022/9212561 -
Reproductive Biology and Endocrinology... Dec 2021Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) activate distinct intracellular signaling cascades. However, due to their similar structure and common...
Recombinant follicular stimulating hormone plus recombinant luteinizing hormone versus human menopausal gonadotropins- does the source of LH bioactivity affect ovarian stimulation outcome?
OBJECTIVE
Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) activate distinct intracellular signaling cascades. However, due to their similar structure and common receptor, they are used interchangeably during ovarian stimulation (OS). This study aims to assess if the source of LH used during OS affects IVF outcome.
PATIENTS AND METHODS
This was a cross sectional study of patients who underwent two consecutive IVF cycles, one included recombinant follicular stimulating hormone (FSH) plus recombinant LH [rFSH+rLH, (Pergoveris)] and the other included urinary hCG [highly purified hMG (HP-hMG), (Menopur)]. The OS protocol, except of the LH preparation, was identical in the two IVF cycles.
RESULTS
The rate of mature oocytes was not different between the treatment cycles (0.9 in the rFSH+rLH vs 0.8 in the HP-hMG, p = 0.07). Nonetheless, the mean number of mature oocytes retrieved in the rFSH+rLH treatment cycles was higher compared to the HP-hMG treatment cycles (10 ± 5.8 vs 8.3 ± 4.6, respectively, P = 0.01). Likewise, the mean number of fertilized oocytes was higher in the rFSH+rLH cycles compared with the HP-hMG cycles (8.5 ± 5.9 vs 6.4 ± 3.6, respectively, p = 0.05). There was no difference between the treatment cycles regarding the number of top-quality embryos, the ratio of top-quality embryos per number of oocytes retrieved or fertilized oocytes or the pregnancy rate.
CONCLUSION
The differences in treatment outcome, derived by different LH preparations reflect the distinct physiological role of these molecules. Our findings may assist in tailoring a specific gonadotropin regimen when assembling an OS protocol.
Topics: Adult; Cross-Sectional Studies; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins; Treatment Outcome
PubMed: 34886872
DOI: 10.1186/s12958-021-00853-7 -
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 -
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 -
Computational and Mathematical Methods... 2022To ask lots of questions and try to find the truth about the medicine-based effectiveness of letrozole (LE) combined with human menopausal gonadotropin (HMG) in the...
Efficacy of Letrozole Combined with Urinary Gonadotropin for Ovulation Induction in Endocrine Abnormal Infertility Patients: A Retrospective Single-Center, Case-Control Study.
AIMS
To ask lots of questions and try to find the truth about the medicine-based effectiveness of letrozole (LE) combined with human menopausal gonadotropin (HMG) in the treatment of inability to have children crops patients with endocrine (things that are different from what is usually expected and the effect on ovulation-related chemicals produced by the body).
MATERIALS AND METHODS
A total of 160 unable to have children crops patients with endocrine things that are different from what is usually expected who were treated in our hospital from March 2019 to March 2022 were selected as the subjects of this look at how things were in the past study and were divided into instance of watching, making a statement group was treated with human menopausal gonadotropin on the basis of the control group. The differences in serum related to the process of making children, chemical produced by the body levels, ovarian function, and ovulation induction effect between the two groups were watched and compared.
RESULTS
After treatment, LH, FSH, PRL, and E in the observation group were better than those in the control group. The ovarian volume, follicle size, follicle diameter, and endometrial thickness of the two groups of patients were significantly improved, and the observation group was better than the control group. Significance is < 0.05. After treatment, the ovarian volume, follicle size, follicle diameter, and endometrial thickness in the two groups were significantly improved, and the observation group was better than the control group, and the difference was statistically significant ( < 0.05). The ovulation rate, pregnancy rate, singleton pregnancy rate, and multiple pregnancy rate of the observation group were higher than those of the control group, and the difference was statistically significant by the chi-square test ( < 0.05).
CONCLUSION
Letrozole can promote the improvement of sex hormones in infertile patients. After being combined with human menopausal gonadotropin treatment, the follicle development and ovulation of patients are significantly improved, and infertility is improved to a certain extent. It has a certain reference value in the clinical treatment of endocrine abnormal infertility.
Topics: Case-Control Studies; Child; Female; Gonadotropins; Humans; Infertility, Female; Letrozole; Menotropins; Ovulation Induction; Pregnancy; Retrospective Studies
PubMed: 35860181
DOI: 10.1155/2022/5363754 -
Frontiers in Endocrinology 2021To assess and compare the feasibility of progestin-primed ovarian stimulation (PPOS) protocol with mild stimulation protocol for advanced age women with diminished... (Comparative Study)
Comparative Study
Progestin-Primed Ovarian Stimulation Versus Mild Stimulation Protocol in Advanced Age Women With Diminished Ovarian Reserve Undergoing Their First Fertilization Cycle: A Retrospective Cohort Study.
OBJECTIVE
To assess and compare the feasibility of progestin-primed ovarian stimulation (PPOS) protocol with mild stimulation protocol for advanced age women with diminished ovarian reserve (DOR) undergoing their first fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle.
METHODS
Patients aged ≥35 years and DOR undergoing their first IVF/ICSI cycle were enrolled in this retrospective cohort study: 139 and 600 patients underwent the PPOS and mild stimulation protocols, respectively. The primary outcomes were cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR). The secondary outcomes were the number of oocytes retrieved and top-quality embryos.
RESULTS
There was nearly no significant difference of baseline characteristics between the two groups. Although a greater amount of total gonadotropin (1906.61 ± 631.04 IU vs. 997.72 ± 705.73 IU, <0.001) and longer duration of stimulation (9 (10-7) vs. 6 (8-4), <0.001) were observed in the PPOS group, the number of retrieved oocytes (3 (6-2) vs. 2 (4-1), <0.001) and top-quality embryos (1 (2-0) vs. 1 (2-0), =0.038) was greater in the PPOS group than the mild stimulation group. Meanwhile, the incidence of premature luteinizing hormone (LH) surge rate was significantly lower in the PPOS group (0.7% vs.8.3%, =0.001) than the mild stimulation group. However, there was no significant difference in conservative CCPR, conservative CLBR, optimistic CCPR, and optimistic CLBR between the two groups (all >0.05). A multivariate logistic regression model showed significant positive effects of the number of retrieved oocytes and number of top-quality embryos on conservative CCPR (OR=1.236, 95%CI: 1.048-1.456, =0.012, OR=2.313, 95%CI: 1.676-3.194, <0.001) and conservative CLBR (OR=1.250, 95%CI: 1.036-1.508, =0.020, OR=2.634, 95%CI: 1.799-3.857, <0.001) respectively, while significant negative effects of age were identified for conservative CCPR (OR=0.805, 95%CI: 0.739-0.877, <0.001) and conservative CLBR (OR=0.797, 95%CI: 0.723-0.879, <0.001).
CONCLUSION
The PPOS protocol is an effective alternative to the mild stimulation protocol for advanced age patients with DOR, as it provides comparable reproductive outcomes and better control of premature LH surge. Further, more oocytes and top-quality embryos were obtained in the PPOS group, which had a positive association with conservative CCPR and CLBR.
Topics: Adult; Chorionic Gonadotropin; Clomiphene; Cohort Studies; Dydrogesterone; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Letrozole; Live Birth; Maternal Age; Medroxyprogesterone Acetate; Menotropins; Odds Ratio; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovarian Reserve; Ovulation Induction; Pregnancy; Pregnancy Rate; Progestins; Retrospective Studies; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate
PubMed: 35140685
DOI: 10.3389/fendo.2021.801026 -
JBRA Assisted Reproduction Apr 2022To compare the number of oocytes obtained in the follicular puncture of high- responder oocyte donors, submitted to ovarian stimulation for in vitro fertilization (IVF)...
OBJECTIVE
To compare the number of oocytes obtained in the follicular puncture of high- responder oocyte donors, submitted to ovarian stimulation for in vitro fertilization (IVF) in two different protocols: Friendly and Conventional.
METHODS
There were one hundred-and-eight infertile egg-donor women, aged between 21 and 35 years, undergoing IVF in this retrospective cohort study. The women were divided into two groups: 1) Friendly protocol: controlled ovarian stimulation (COS) with corifollitropin alpha, clomiphene citrate and dydrogesterone without daily rFSH (n=52) and 2) In the Conventional protocol, we had COS with menotropin daily and ganirelix (n=66). We assessed age, body mass index, time and cause of infertility, antral follicle count (AFC) by three-dimensional ultrasound, number of visits to the clinic, COS duration, number of follicles ≥14mm on the trigger day, early ovulation frequency, number of mature oocytes, number of cryopreserved embryos, clinical pregnancy rate, frequency of OHSS.
RESULTS
The ovulatory factor was higher in women in the Conventional protocol (p=0.03), and the tubal factor (p=0.02) was higher in the Friendly protocol group. The number of visits to the clinic was lower among women in the Friendly protocol (p=0.04). The number of mature eggs, the clinical pregnancy rate and the frequency of OHSS were similar between the groups. The number of frozen embryos was higher in the Friendly group (p=0.02). The regression model demonstrated that the ovulatory factor, the tubal factor and the number of visits to the clinic were not predictors of the number of mature oocytes. Only AFC was an independent predictor of the number of meiosis II oocytes (p<0.01).
CONCLUSIONS
The Friendly protocol seems to be as safe and effective as the Conventional protocol for infertile high-responder oocyte donors, resulting in a similar number of mature oocytes and OHSS incidence.
Topics: Clomiphene; Dydrogesterone; Female; Fertilization in Vitro; Humans; Infertility, Female; Oocytes; Ovulation Induction; Pregnancy; Retrospective Studies
PubMed: 34672261
DOI: 10.5935/1518-0557.20210082