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The Cochrane Database of Systematic... Feb 2011hMG and recombinant FSH, have both been used successfully for controlled ovarian hyperstimulation in in vitro fertilization and embryo transfer (IVF-ET). (Review)
Review
BACKGROUND
hMG and recombinant FSH, have both been used successfully for controlled ovarian hyperstimulation in in vitro fertilization and embryo transfer (IVF-ET).
OBJECTIVES
To compare the effectiveness of hMG with rFSH in ovarian stimulation protocols in IVF or ICSI treatment cycles.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 3rd Jan 2002), PubMed, MEDLINE, Web of Science (all searched 1985 to May 15 2002), and reference lists of articles. We also contacted manufacturers and researchers in the field.
SELECTION CRITERIA
Randomised trials comparing hMG with rFSH for ovarian stimulation in IVF or ICSI treatment for treatment of infertility in normogonadotrophic women.
DATA COLLECTION AND ANALYSIS
The main outcome measure was ongoing pregnancy/live birth per woman.Secondary outcomes included total gonadotrophin dose used, cancellation, number of oocytes retrieved, implantation, clinical pregnancy per woman, multiple pregnancy, spontaneous abortion and ovarian hyperstimulation syndrome. Peto odds ratios (OR) for hMG relative to rFSH were calculated after testing for homogeneity of treatment effect across all trials. Analyses were performed separately for the three different GnRHa protocols used: (1) without GnRHa down-regulation, (2) with GnRHa down-regulation using a short protocol and (3) with GnRHa down-regulation using a long protocol.
MAIN RESULTS
Eight trials that met the inclusion criteria could be identified. One trial did not use down-regulation, one trial used a short protocol and six trials used a long down-regulation protocol. In the one trial with non-down-regulated women and in the one trial that used a short down-regulation protocol there was no evidence of a difference between hMG and rFSH in any clinical outcome. Data of four truly randomised trials in women down-regulated using a long protocol could be pooled. There was no evidence of a difference between hMG and rFSH in ongoing pregnancy/live birth per woman (OR 1.27; 95% CI 0.98 to 1.64). Furthermore there was no clear difference on any of the secondary outcomes, although the clinical pregnancy rate per woman was of borderline significance in favour of hMG (summary OR 1.28; 95% CI 1.00 to 1.64). The other secondary outcomes were comparable for both gonadotrophins.
AUTHORS' CONCLUSIONS
For all three GnRHa protocols analysed there is insufficient evidence of a difference between hMG and rFSH on ongoing pregnancy or live birth. More large randomised trials are needed to estimate the difference between hMG and rFSH more precisely. Such trials should preferably (1) use a consistent long GnRHa protocol and (2) use a fixed dose of gonadotrophin such to prevent potentially subjective decisions of the clinician in dosing and (3) take live birth as primary endpoint. At this moment in time however, in prescribing gonadotrophins for ovarian hyperstimulation in IVF one should use the least expensive medication.
Topics: Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gamete Intrafallopian Transfer; Humans; Menotropins; Ovulation Induction; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 21328264
DOI: 10.1002/14651858.CD003973.pub2 -
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 -
Fertility and Sterility Jan 1996To assess the efficacy of IVP-ET in infertile women with the polycystic ovary syndrome (PCOS) and to provide a comprehensive review of contemporary therapeutic options... (Review)
Review
OBJECTIVE
To assess the efficacy of IVP-ET in infertile women with the polycystic ovary syndrome (PCOS) and to provide a comprehensive review of contemporary therapeutic options and their complications as reflected in the current literature.
DESIGN
Pertinent studies in medical literature identified through computerized bibliographic search and via manual review of relevant scientific publications.
RESULTS
In vitro fertilization and ET is an effective therapy for PCOS patients who are refractory to ovulation induction in vivo or who have coexisting infertility factors. The use of GnRH agonist (GnRH-a) is associated with significant reductions in the incidence of pregnancy loss and may improve fertilization and cleavage rates. In the PCOS patient, the use of purified FSH preparations does not appear to improve pregnancy rates nor other clinical parameters when compared with hMG. Severe ovarian hyperstimulation syndrome (OHSS) is an important consideration when PCOS patients undergo superovulation protocols. Strategies for OHSS prevention include the use of intravenous albumin immediately after oocyte retrieval, triggering of ovulation with a GnRH-a, or withholding menotropin therapy for several days before hCG administration. Cryopreservation of all embryos for future transfer in an artificial cycle has also proven to be an effective alternative in PCOS patients at high risk for severe OHSS.
CONCLUSIONS
Pregnancy rates for PCOS patients undergoing IVF-ET are comparable with those for women with tubal factor infertility. Therefore, IVF-ET should be offered to patients with PCOS who are refractory to conventional infertility modalities.
Topics: Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Leuprolide; Menotropins; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Pregnancy; Triptorelin Pamoate
PubMed: 8557121
DOI: 10.1016/s0015-0282(16)58017-0 -
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 -
The Cochrane Database of Systematic... 2000To conduct a systematic overview of available data comparing FSH and hMG in IVF treatment cycles. (Review)
Review
OBJECTIVES
To conduct a systematic overview of available data comparing FSH and hMG in IVF treatment cycles.
SEARCH STRATEGY
This review has drawn on the search strategy developed for the Subfertility Group as a whole. Relevant trials were identified in the Group's Specialised Register of Controlled Trials. See Review Group details for more information.
DATA COLLECTION AND ANALYSIS
A systematic review and meta-analysis of randomized trials of FSH versus hMG use in ovarian stimulation protocols, with or without GnRH agonists, in IVF treatment cycles. Common odds ratios (OR) were calculated after demonstrating homogeneity of treatment effect across all trials.
MAIN OUTCOME MEASURES
Clinical pregnancy rates per cycle started, per cycle reaching oocyte retrieval, and per cycle reaching embryo transfer (ET).
RESULTS
Eight trials met the inclusion criteria. The overall OR in favour of FSH for cycle start, oocyte retrieval, and ET were 1.70 (95% CI, 1.11-2.60), 1.68 (95% CI, 1.10-2.56), and 1.69 (95% CI, 1.10-2.59), respectively.
REVIEWER'S CONCLUSIONS
This meta-analysis demonstrates that in IVF cycles the use of FSH is associated with a significantly higher clinical pregnancy rate than hMG.
Topics: Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Menotropins; Ovulation Induction; Pregnancy
PubMed: 10796481
DOI: 10.1002/14651858.CD000061 -
Obstetrics and Gynecology Apr 1996To examine the production and immunolocalization of interleukin-6 (IL-6) in patients with the ovarian hyperstimulation syndrome.
OBJECTIVE
To examine the production and immunolocalization of interleukin-6 (IL-6) in patients with the ovarian hyperstimulation syndrome.
METHODS
The study group consisted of patients with ovarian hyperstimulation syndrome (n = 9) from whom serum and ascites samples were obtained. The control samples used were serum (n = 10) and peritoneal (n = 16) and follicular fluids (n = 8) from healthy individuals. Follicular fluid (n = 40) and serial serum samples were also obtained from patients undergoing menotropin stimulation for in vitro fertilization (IVF) before (n = 10) and after ovulation (n = 34). Interleukin-6 measurements were performed with a sensitive immunoassay and confirmed with a bioassay. Immunohistochemical localization of IL-6 was performed with a mouse monoclonal antibody in normal premenopausal (n = 5) and postmenopausal ovaries (n = 5), as well as with cells from stimulated follicular fluid aspirates (n = 3).
RESULTS
We found significantly higher serum and ascites IL-6 levels in ovarian hyperstimulation syndrome (mean 18.8 +/- 1.1 and 810.8 +/- 60.7 pg/mL, respectively) compared with postovulatory serum and peritoneal fluid from normal controls (mean 4.4 +/- .69 and 44.7 +/- 7.5 pg/mL, respectively) (P < .001) or serum after menotropin stimulation (13.1 +/- 1.1 pg/mL) (P < .001). At the time of ovulation, follicular fluid IL-6 levels (normal controls, mean 9 +/- 2.1 pg/mL; menotropin stimulation, mean 10.1 +/- 4 pg/mL) were higher than in preovulatory serum (normal controls, mean 4.5 +/- .8 pg/mL; menotropin stimulation, mean 6.3 +/- 1.4 pg/mL) (P < .001). Immunohistochemical localization of IL-6 revealed intense staining in corpora lutea and theca cells from large antral follicles and luteinized granulosa cells in follicular aspirates after menotropin stimulation.
CONCLUSION
Interleukin-6 levels are markedly elevated in the ovarian hyperstimulation syndrome when compared with controls. The higher follicular fluid IL-6 levels seen suggest local secretion of this cytokine. Immunohistochemical correlation demonstrated IL-6 within ovarian theca cells. These findings suggest a local role for IL-6 both in normal and stimulated ovarian function. Whether IL-6 is directly responsible for the clinical manifestations of this syndrome is unclear. However, when produced in massive amounts, the pro-inflammatory effects of IL-6 may contribute to its pathogenesis and perhaps serve as a marker for the disease.
Topics: Adult; Animals; Ascitic Fluid; Biological Assay; Female; Humans; Immunoassay; Immunohistochemistry; Interleukin-6; Menotropins; Mice; Ovarian Hyperstimulation Syndrome
PubMed: 8602312
DOI: 10.1016/0029-7844(95)00456-4 -
British Medical Journal May 1979A simple scheme of investigation and treatment to restore fertility in amenorrhoeic women is described. Fifty-nine patients with amenorrhoea not due to primary ovarian... (Review)
Review
A simple scheme of investigation and treatment to restore fertility in amenorrhoeic women is described. Fifty-nine patients with amenorrhoea not due to primary ovarian failure were treated variously as appropriate, mainly with clomiphene (25), bromocriptine (15), or human menopausal gonadotrophins (12), and six by diet to increase their weight. All ovulated, and by the end of the study 55 (93%) had conceived, 42 (71%) had delivered at least one surviving child, and five others (8%) were pregnant and awaiting delivery. Conception rates were 49% within two cycles of treatment and 66% within three cycles; using life-table method to standardise the cumulative conception rates by correcting for patients who did not continue as long as others in the study, the expected conception rate was 79% in six cycles, 94% in 12 cycles, and 98% after 16 cycles. The multiple pregnancy rate was 13% and abortion rate 22%. Delivery rate (for a viable baby) were 48% within 11 months of starting treatment and 53% within one year; expected rates were 76% in 18 months and 97% in two years. The results show that a relatively simple scheme of classifying amenorrhoeic disorders endocrinologically followed by treatment directed at inducing ovulation allows amenorrhoeic women without primary ovarian failure to achieve conception and delivery rates equal to those in normal women.
Topics: Adult; Amenorrhea; Body Weight; Bromocriptine; Clomiphene; Female; Fertility; Fertility Agents, Female; Fertilization; Humans; Menotropins; Ovulation Induction; Pregnancy; Pregnancy, Multiple; Time Factors
PubMed: 378318
DOI: 10.1136/bmj.1.6173.1257 -
Fertility and Sterility Dec 1978The plasma hormonal patterns of the normal menstrual cycle have been reviewed. A consistent cyclic pattern of plasma hormone levels is observed in LH, FSH, estrogens,...
The plasma hormonal patterns of the normal menstrual cycle have been reviewed. A consistent cyclic pattern of plasma hormone levels is observed in LH, FSH, estrogens, and progestins in the menstrual cycle. Other plasma hormones, such as ACTH, growth hormone, TSH, and PRL, as well as androgens and corticosteroids, fluctuate throughout the menstrual cycle without any consistent pattern during the ovulatory cycle. FSH, LH, E2, E1, P, T, and A levels during the induced ovulatory cycle are presneted for comparison. In the gonadotropin-induced ovulatory cycle most hormones behave in a manner similar to that in the normal ovulatory cycle, except for FSH levels, which rise continuously throughout the follicular phase of the cycle. Following ovulation in the gonadotropin-induced cycle, T rises above normal levels. Early in the clomiphene-induced ovulatory cycle, unlike the normal cycle, LH is distinctly elevated. Levels of both LH and FSH in the rest of the cycle simulate those in the normal cycle. However, T and A levels rise from the very beginning of clomiphene therapy and continue to rise throughout the clomiphene-induced ovulatory cycle. Levels of E and P are higher than in the normal ovulatory cycle, but a similar pattern is preserved. Because of the potential dangers of gonadotropin therapy, monitoring by frequent examination and laboratory tests is required. E monitoring is mandatory to evaluate follicular maturation, to time hCG administration, and to minimize hyperstimulation. Cervical mucus is an unreliable parameter for monitoring gonadotropin therapy alone. In addition to cervical mucus, plasma or urinary E should be monitored regularly. Clomiphene therapy is less dangerous than gonadotropin therapy. Because of its lesser risk, monitoring is rarely performed during clomiphene use. An active monitoring approach has been described. While this approach may not necessarily improve the outcome of clomiphene therapy, it may hasten the process of selecting the appropriate dose. Although other ovulation-inducing agents are available, their use is rarely associated with serious medical complications, and monitoring would seem unnecessary.
Topics: Cervix Mucus; Chorionic Gonadotropin; Clomiphene; Estradiol; Estrogens; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Menstruation; Monitoring, Physiologic; Ovulation Induction; Progesterone
PubMed: 729822
DOI: 10.1016/s0015-0282(16)43649-6 -
Fertility and Sterility Jan 1991From the reviewed data, it appears that CC, hMG-hCG, or the association of these drugs with IVF-ET and GIFT programs do not carry an increased risk for congenital... (Review)
Review
Early miscarriage and fetal malformations after induction of ovulation (by clomiphene citrate and/or human menotropins), in vitro fertilization, and gamete intrafallopian transfer.
From the reviewed data, it appears that CC, hMG-hCG, or the association of these drugs with IVF-ET and GIFT programs do not carry an increased risk for congenital malformations as a whole, nor is there any specific malformation that has an increased incidence or is related in any way with the use of these drugs. Table 7 represents the specific malformation rate per 1,000 births in the general population and in newborns delivered after treatment with CC, hMG-hCG, or IVF-ET and GIFT. The malformation rate in the treated groups does not differ from that of the general population. However, as shown by McIntosh et al., the incidence of congenital malformations often rises with a longer follow-up. Most of the reports about babies born after ovulation induction are based on the initial examination done shortly after birth. Thus, studies including examination of these infants up to at least 12 months of age will be undoubtedly of value. Also, data concerning the reproductive capability of women born after ovulation induction is lacking. With regard to the abortion rate in pregnancies achieved after such treatments and procedures, it can be concluded that it does not appear to be higher than that of the general population, particularly when early pregnancy loss, advanced maternal age, the infertility status, and the increased incidence of multiple pregnancies occurring in these patients are taken into consideration.
Topics: Abortion, Spontaneous; Clomiphene; Congenital Abnormalities; Female; Fertilization in Vitro; Gamete Intrafallopian Transfer; Humans; Menotropins; Ovulation Induction; Pregnancy
PubMed: 1898885
DOI: 10.1016/s0015-0282(16)54048-5 -
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