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Reproductive Biology and Endocrinology... Jul 2018The association of recombinant FSH plus recombinant LH in 2:1 ratio may be used not only to induce ovulation in anovulatory women with hypogonadotropic hypogonadism but...
Probabilistic cost-effectiveness analysis of controlled ovarian stimulation with recombinant FSH plus recombinant LH vs. human menopausal gonadotropin for women undergoing IVF.
BACKGROUND
The association of recombinant FSH plus recombinant LH in 2:1 ratio may be used not only to induce ovulation in anovulatory women with hypogonadotropic hypogonadism but also to achieve multiple follicular developments in human IVF. The aim of this analysis was to estimate the cost-effectiveness of Controlled Ovarian Stimulation (COS) with recombinant FSH (rFSH) plus recombinant LH (rLH) in comparison with highly purified human menopausal gonadotropin (HP-hMG) in the woman undergoing in vitro fertilization (IVF) in Italy.
METHODS
A probabilistic decision tree was developed to simulate patients undergoing IVF, either using r-FSH + r-LH or HP-hMG to obtain COS. The model considers the National Health System (NHS) perspective and a time horizon equal to two years. Simulations were reported considering the number of retrieved oocytes (5-9, 10-15 and > 15) and transition probabilities were estimated through specific analyses carried out on the population of 848 women enrolled in the real-life.
RESULTS
The model estimated that patients undertaking therapeutic protocol with r-FSH + r-LH increase the general success rate (+ 6.6% for pregnancy). The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) of r-FSH + r-LH was below the willingness to pay set at €20,000 for all the considered scenarios.
CONCLUSIONS
The cost-utility analysis demonstrated that the r-FSH + r-LH is a cost-effective option for the Italian National Health System (NHS).
Topics: Costs and Cost Analysis; Decision Trees; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Pregnancy; Pregnancy Rate; Quality of Life
PubMed: 30021630
DOI: 10.1186/s12958-018-0386-2 -
The Journal of International Medical... Jun 2018Objective To compare the efficacy of three protocols for ovarian stimulation in patients with diminished ovarian reserve during in vitro fertilization (IVF) treatment.... (Comparative Study)
Comparative Study Randomized Controlled Trial
Objective To compare the efficacy of three protocols for ovarian stimulation in patients with diminished ovarian reserve during in vitro fertilization (IVF) treatment. Methods This prospective randomized study enrolled patients with diminished ovarian reserve who underwent cycles of IVF or intracytoplasmic sperm injection. The patients were randomly divided into three groups: a modified gonadotrophin releasing hormone (GnRH) agonist protocol (group A); (ii) a mild stimulation protocol (group B); or (iii) an antagonist protocol (group C). Demographic characteristics, clinical variables and pregnancy outcomes were compared between the groups. Results A total of 116 patients were enrolled in the study: 54 in group A, 52 in group B and 60 in group C. Group B (32.69%) had a significantly higher cycle cancellation rate compared with groups A (11.11%) and C (16.67%). The early abortion rate of group C (44.44%) was significantly higher than group A (12.50%), but not significantly different from group B (16.67%). There were no significant differences in the clinical pregnancy rates and live birth rates among the three groups. Conclusion A modified GnRH agonist protocol achieved a comparable pregnancy rate to those of the mild stimulation protocol and antagonist protocol, whilst having lower cycle cancellation and early abortion rates.
Topics: Adult; Clinical Protocols; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Letrozole; Luteolytic Agents; Male; Menotropins; Ovarian Follicle; Ovarian Reserve; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Sperm Injections, Intracytoplasmic; Treatment Outcome; Triptorelin Pamoate
PubMed: 29695208
DOI: 10.1177/0300060518770346 -
Taiwanese Journal of Obstetrics &... Apr 2018To compare the influences of controlled ovarian hyperstimulation (COH) drugs using recombinant follicular stimulating hormone (rFSH) versus human menopausal...
OBJECTIVE
To compare the influences of controlled ovarian hyperstimulation (COH) drugs using recombinant follicular stimulating hormone (rFSH) versus human menopausal gonadotropins (hMG) on morphometry and morphology of MII oocytes in ICSI cycles.
MATERIALS AND METHODS
In this prospective study, 363 MII oocytes from 50 ICSI cycles with male factor infertility were evaluated. The patients were divided into two groups according to the protocols of COH: I- rFSH and II- hMG. The immature oocytes were excluded from the study. All oocytes were categorized into four morphological groups of normal, and those with single, double, or multiple defects. The inclusive morphometrical criteria were: areas and diameters of oocyte, ooplasm, and zona pellucida (ZP). Also, circumferences of oocyte and ooplasm were assessed.
RESULTS
The ZP area and ooplasm diameter for both normal and abnormal oocytes were significantly higher in group I (P: .05; P: .028, respectively) compared to group II (P: .023; P: .003, respectively). In abnormal oocytes, ooplasm diameter was higher in group I compared to group II. Furthermore, ooplasm area for abnormal oocytes was significantly higher in group I compared to group II. There was an increasing trend for number of mature oocytes, in abnormal oocytes, for group I (5.53 ± 3.1) in comparison with group II (4.4 ± 2.97; P = .25). The rate of oocytes with normal morphology was significantly higher in hMG, when compared to rFSH groups.
CONCLUSION
Morphometrical parameters were increased in rFSH group, but the normal morphology of oocytes were significantly enhanced in hMG group. Treatment with proper dosage of ovulation induction drugs may enhance the number of normal sized oocytes.
Topics: Cell Size; Female; Follicle Stimulating Hormone; Humans; Infertility, Male; Male; Menotropins; Oocytes; Ovulation Induction; Prospective Studies; Recombinant Proteins; Sperm Injections, Intracytoplasmic; Zona Pellucida
PubMed: 29673662
DOI: 10.1016/j.tjog.2018.02.007 -
Scientific Reports Mar 2018Medroxyprogesterone 17-acetate (MPA) combined with human menopausal gonadotropin (hMG) has been effectively used for ovarian stimulation in clinical practice. However,...
Medroxyprogesterone 17-acetate (MPA) combined with human menopausal gonadotropin (hMG) has been effectively used for ovarian stimulation in clinical practice. However, the molecular mechanism of MPA + hMG treatment in follicular development is poorly described. Here we performed a study to investigate the impact of MPA + hMG on ovarian stimulation utilizing a mouse model in vivo. Forty female BALB/C mice were randomly divided into four groups of 10 each and treated during ciestrus stage and continued for 5 days: control group, MPA group, hMG group, and MPA + hMG group. Morphological and molecular biology methods were used for detecting serum hormones and ovarian function. MPA + hMG group exhibited increasing follicle stimulating hormone (FSH), antral follicle, FSH receptor (FSHR) and phosphorylated mammal target of rapamycin (p-mTOR), and decreasing luteinizing hormone (LH), estradiol (E2), progesterone (P), corpus luteum, phosphoinositide 3-kinase (PI3K), Akt and mTOR compared with control group. In contrast, MPA + hMG group showed reduced FSH, LH, E2, P, corpus luteum, LH receptor (LHR), and activated PI3K,/Akt/mTOR pathway compared with hMG group (P < 0.05). Collectively, these data definitively established that MPA plus hMG may modulate the hormone, hormone receptor and PI3K/Akt/mTOR signaling pathway to influence follicular development in the mouse ovary. Our study provides overwhelming support for MPA + hMG as an effective treatment for infertility in women.
Topics: Animals; Disease Models, Animal; Female; Hormones; Humans; Medroxyprogesterone Acetate; Menopause; Menotropins; Mice; Mice, Inbred BALB C; Ovarian Follicle; Ovulation Induction; Random Allocation; Signal Transduction; Treatment Outcome
PubMed: 29535409
DOI: 10.1038/s41598-018-22797-6 -
Journal of the Formosan Medical... Jan 2019The role of LH during controlled ovarian stimulation (COS) in the general population remains contentious. There is no consensus on the indications for LH supplementation...
BACKGROUND/PURPOSE
The role of LH during controlled ovarian stimulation (COS) in the general population remains contentious. There is no consensus on the indications for LH supplementation during COS. The purpose of this study is to determine whether menotropin supplement is associated with decreases in early pregnancy loss rates in patients exhibiting low endogenous LH during COS.
METHOD
This is a single-center, retrospective cohort from a university-affiliated hospital. Patients were enrolled from the in-vitro fertilization center from January, 2011 to December, 2014. Patients who experienced a LH level ≦ 0.8 mIU/mL during stimulation were identified, and patients that received menotropin supplementation were compared to those without menotropin supplementation. Outcome variables, including the number of oocytes retrieved, embryos obtained, implantation rates, pregnancy rates and early pregnancy loss rates, were compared.
RESULTS
Patients that experienced low LH during GnRH antagonist protocol and were supplemented with menotropin were associated with lower early pregnancy loss when compared with patients without menotropin supplementation (26.7% vs. 11.5%, p = 0.045). More specifically, in patients who exhibited early-onset low LH, before the use of GnRH antagonists, menotropin supplementation was associated with significantly lower early pregnancy loss compared with non-supplemented patients (3.3% vs. 29.0%, OR: 0.08, p = 0.012). Beneficial effects persisted after adjusting for confounders (aOR: 0.103, 95% CI: 0.011-0.933).
CONCLUSION
Menotropin supplementation is associated with decreased early pregnancy loss in patient who exhibited low LH during GnRH antagonist cycles. This effect is especially prominent in patients who experience low LH before the start of GnRH antagonists.
Topics: Abortion, Spontaneous; Adult; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Logistic Models; Luteinizing Hormone; Menotropins; Multivariate Analysis; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Taiwan
PubMed: 29402595
DOI: 10.1016/j.jfma.2018.01.012 -
BMC Research Notes Jan 2018The aim of the study was to assess the lower limits of midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed...
Minimum values for midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or intrauterine insemination without a human menopausal gonadotropin.
OBJECTIVE
The aim of the study was to assess the lower limits of midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or intrauterine insemination without a human menopausal gonadotropin stimulation.
RESULTS
We included 297 pregnant cycles of 297 women and assessed midluteal plasma progesterone and estradiol concentrations and pregnancy outcomes, retrospectively. These cycles were compared with the non-pregnant cycles (406 cycles) of the same women who became pregnant. Mean midluteal plasma P4 and E2 concentrations were significantly (P < 0.01) higher in pregnant cycles (14.5 and 188.5 pg/mL) than in non-pregnant cycles (10.7 and 162.6 pg/mL). The 5 percentiles of progesterone and estradiol in pregnant cycles were 5.6 and 70.2 pg/mL, respectively. The lowest progesterone and estradiol levels in pregnant cycles were 2.3 and 23.4 pg/mL, respectively. In non-pregnant cycles, many women had low P4 levels that were less than 5.6 ng/mL. Subgroup analyses showed slight differences among the four groups, which may have been due to the ovarian function of each group. Miscarriage was not related to progesterone and estradiol concentrations. These values may be useful for the evaluation of necessary values for pregnancy with timed intercourse or intrauterine insemination.
Topics: Adult; Coitus; Estradiol; Female; Humans; Insemination; Luteal Phase; Menotropins; Ovulation; Pregnancy; Pregnancy Outcome; Progesterone
PubMed: 29357944
DOI: 10.1186/s13104-018-3188-x -
Journal of Assisted Reproduction and... Dec 2017The aim of this study is to determine whether a clinical advantage is gained with use of LH in combination with FSH or as a component of human menopausal gonadotropin...
PURPOSES
The aim of this study is to determine whether a clinical advantage is gained with use of LH in combination with FSH or as a component of human menopausal gonadotropin (hMG) to achieve optimal ovarian stimulation.
METHODS
In this study, we compared retrospectively two regimens, r-FSH/r-LH and hMG, for the treatment of women with reduced ovarian reserve, identified as subjects with antral follicle count (AFC) < 11 and AMH ≤ 1.1 ng/ml.
RESULTS
Overall, the clinical pregnancy per started cycle was higher in the r-FSH/r-LH group (12.5 vs. 8.1%, P < 0.02), while implantation (11.1 vs. 9.5%) and miscarriage rates (29.9 vs. 35.9%) were comparable. Data were further analysed performing separate comparisons in subpopulations with different ranges of AFC, i.e. < 4, 4-6 and 7-10. Major differences between the two regimens were observed in women with AFC < 4. In this subpopulation, not only was the clinical pregnancies per started cycle higher in the r-FSH/r-LH group (10.2 vs. 1.5%, P < 0.01), but also implantation was significantly higher (13.0 vs. 2.8%, P < 0.02).
CONCLUSIONS
A r-FSH/r-LH regimen appears to be beneficial for the treatment of women with extremely poor ovarian reserve. It should be considered however that, being retrospective, this study is affected by obvious limitations, such as post-treatment patient selection criteria and absence of randomisation.
Topics: Adult; Embryo Implantation; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovarian Reserve; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Recombinant Proteins; Retrospective Studies
PubMed: 28871409
DOI: 10.1007/s10815-017-1034-z -
Journal of Physiology and Pharmacology... Jun 2017The aim of the study was to assess the predictive value of vascular endothelial growth factor (VEGF), its soluble receptor - sVEGF-R1/sFlt1 and endocrine gland-derived... (Observational Study)
Observational Study
High levels of soluble vascular endothelial growth factor receptor 1/sFlt1 and low levels of vascular endothelial growth factor in follicular fluid on the day of oocyte retrieval correlate with ovarian hyperstimulation syndrom regardless of the stimulation protocol.
The aim of the study was to assess the predictive value of vascular endothelial growth factor (VEGF), its soluble receptor - sVEGF-R1/sFlt1 and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) concentrations in serum and follicular fluid (FF) for ovarian hyperstimulation syndrome (OHSS) in women undergoing controlled ovarian hyperstimulation (COH) protocols. Patients have been divided into 3 groups: control group on natural cycle, patients stimulated with GnRH agonist and patients stimulated with GnRH antagonist. The FF and serum concentrations of VEGF, EG-VEGF, sVEGF R1 and the expression of VEGF and EG-VEGF mRNA in GC in small and large follicles collected from patients were investigated. When we compared all patients in a trial, OHSS occurrence was correlated with higher level of sVEGF R1 and a lower level of VEGF in a follicular fluid from large follicles in a day of oocyte retrieval. The VEGF/sVEGF-R1 ratio for patients in COH groups, above which the risk of developing OHSS is very low (OR 0.1 (95% CI 0.01 - 0.29, P = 0.0006) was found to be 0.281 pg/ml, with AUC - 0.738, P = 0.042, (95% CI 0.656 - 0.82). High levels of sVEGF-R1 and low level of VEGF in FF on the day of oocyte retrieval correlate with OHSS regardless of the stimulation protocol.
Topics: Adult; Female; Fertilization in Vitro; Follicular Fluid; Gonadotropin-Releasing Hormone; Humans; Menotropins; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; RNA, Messenger; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor, Endocrine-Gland-Derived
PubMed: 28820403
DOI: No ID Found -
Medicine Aug 2017The aim of this study was to explore the effect of clomiphene citrate (CC) on the cycle characteristics and outcomes of obese women with polycystic ovarian syndrome... (Observational Study)
Observational Study
Clomiphene citrate is associated with favorable cycle characteristics but impaired outcomes of obese women with polycystic ovarian syndrome undergoing ovarian stimulation for in vitro fertilization.
The aim of this study was to explore the effect of clomiphene citrate (CC) on the cycle characteristics and outcomes of obese women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation for in vitro fertilization (IVF).This is a retrospective cohort study, and it was conducted at the tertiary-care academic medical center.This study included 174 obese PCOS patients undergoing IVF.In the study group (n = 90), CC and human menopausal gonadotropin (HMG) were administered simultaneously beginning on cycle day 3, while in control group (n = 84) HMG was used only. Both of the 2 groups used medroxyprogesterone acetate (MPA) for preventing premature luteinizing hormone (LH) surges. Ovulation was cotriggered by a GnRH agonist and hCG when dominant follicles matured.The primary outcome measure was the number of oocytes retrieved. Secondary outcomes included the number of top-quality embryos, maturation rate, fertilization rate, cleavage rate, incidence of premature LH surge, and OHSS.The study group received obviously lower total HMG dose [1650 (975-4800) vs 2025 (1350-3300) IU, P = 2.038E-4] but similar HMG duration. While the antral follicle count (AFC) is higher in study group, the number of oocytes retrieved and top-quality embryos are remarkably less [5 (0-30) vs 13 (0-42), P = 6.333E-5; 2 (0-14) vs 3.5 (0-15), P = .003; respectively]. The mature oocyte rate is higher in study group (P = .036). No significant differences were detected in fertilization rate and cleavage rate between 2 groups.CC has a positive influence on cycle characteristics, but might be correlated with the impaired IVF outcomes (less oocytes retrieved and top quality embryos, lower oocyte retrieval rate) in obese PCOS patients undergoing IVF, when HMG and MPA are used simultaneously.
Topics: Academic Medical Centers; Adult; Clomiphene; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility, Female; Medroxyprogesterone Acetate; Menotropins; Obesity; Oocytes; Ovulation Induction; Polycystic Ovary Syndrome; Retrospective Studies
PubMed: 28796038
DOI: 10.1097/MD.0000000000007540