-
Reproductive Biology and Endocrinology... Jun 2021Several studies suggest that luteinizing hormone (LH) could improve IVF outcome in women of advanced reproductive age by optimizing androgen production. In this review,... (Meta-Analysis)
Meta-Analysis
Recombinant human luteinizing hormone co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age: a systematic review and meta-analysis of randomized controlled trials.
INTRODUCTION
Several studies suggest that luteinizing hormone (LH) could improve IVF outcome in women of advanced reproductive age by optimizing androgen production. In this review, we assessed the role of recombinant-human LH (r-hLH) and recombinant human follicle stimulating hormone (r-hFSH) co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age candidates for assisted reproduction.
MATERIAL AND METHODS
Using a preregistered protocol we systematically searched Medline/PubMed, Scopus and the ISI Web of Science databases to identify randomized controlled trials in which r-hFSH monotherapy protocols were compared with r-hFSH/r-hLH co-treatment in women ≥35 years undergoing fresh IVF cycles. We calculated the pooled odds ratio (OR) for dichotomous data and the weight mean difference (WMD) for continuous data with an associated 95% confidence interval (CI). The meta-analyses were conducted using the random-effect model. P values < 0.05 were considered statistically significant. Subgroup analyses of all primary and secondary outcomes were performed only in women aged 35-40 years.
RESULTS
Twelve studies were identified. In women aged between 35 and 40 years, r-hFSH/r-hLH co-treatment was associated with higher clinical pregnancy rates (OR 1.45, CI 95% 1.05-2.00, I = 0%, P = 0.03) and implantation rates (OR 1.49, CI 95% 1.10-2.01, I = 13%, P = 0.01) versus r-hFSH monotherapy. Fewer oocytes were retrieved in r-hFSH/r-hLH-treated patients than in r-hFSH-treated patients both in women aged ≥35 years (WMD -0.82 CI 95% -1.40 to - 0.24, I = 88%, P = 0.005) and in those aged between 35 and 40 years (WMD -1.03, CI - 1.89 to - 0.17, I = 0%, P = 0.02). The number of metaphase II oocytes, miscarriage rates and live birth rates did not differ between the two groups of women overall or in subgroup analysis.
CONCLUSION
Although more oocytes were retrieved in patients who underwent r-hFSH monotherapy, this meta-analysis suggests that r-hFSH/r-hLH co-treatment improves clinical pregnancy and implantation rates in women between 35 and 40 years of age undergoing ovarian stimulation for assisted reproduction technology. However, more RCTs using narrower age ranges in advanced age women are warranted to corroborate these findings.
Topics: Adult; Combined Modality Therapy; Female; Humans; Luteinizing Hormone; Ovulation Induction; Randomized Controlled Trials as Topic; Recombinant Proteins; Reproduction; Reproductive Techniques, Assisted
PubMed: 34154604
DOI: 10.1186/s12958-021-00759-4 -
Journal of Assisted Reproduction and... Sep 2021Although several studies have reported a potential impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on controlled ovarian stimulation (COS), the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Although several studies have reported a potential impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on controlled ovarian stimulation (COS), the results remain controversial. The aim of the systematic review and meta-analysis was to evaluate the effect of MTHFR polymorphism on COS outcomes.
METHODS
PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 2, 2020. COS clinical outcomes based on gene polymorphisms were included. Two reviewers independently extracted the data. The primary outcome was the number of oocytes retrieved. The secondary outcomes were the number of metaphase II (MII) oocytes, stimulation duration, basal follicle-stimulating hormone (FSH) level, FSH dosage, positive pregnancy test, ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Meta-analysis was performed using a fixed-effect model or random-effect model with Review Man 5.3.5. Mean difference (MD) with 95% confidence intervals (95%CIs) was calculated for continuous outcomes. The quality assessment of included studies was evaluated by using the Newcastle-Ottawa Scale.
RESULTS
Eleven studies were included in the systematic review, and seven studies with 2015 participants were included in the meta-analysis. Basal FSH level was significantly lower in CC homozygotes than TT homozygotes (four studies, 867 participants, MD - 0.54, 95%CI - 0.85 to - 0.23, P = 0.0006; I = 0%) of MTHFR (rs1801133). FSH dose was significantly fewer in CC homozygotes compared with CT heterogeneous (three studies, 949 participants, MD - 75.78, 95%CI - 135.23 to - 16.33, P = 0.01; I = 32%) or CT/TT model (three studies, 1097 participants, MD - 80.18, 95%CI - 135.54 to - 24.81, P = 0.005; I = 42%). Differences in the oocytes retrieved and stimulation duration were insignificant. Gene variants on MTHFR (rs1801133) and MTHFR (rs1801131) were reported in ongoing pregnancy rate, clinical pregnancy rate, and live birth rate.
CONCLUSION
Studies to date indicate that polymorphisms of MTHFR could influence basal FSH level and FSH dose. The results could be useful to promote clinical practice on COS protocols. Further studies are needed to evaluate the clinical relevance of the multigene combination on COS.
Topics: Birth Rate; Female; Humans; Infertility, Female; Methylenetetrahydrofolate Reductase (NADPH2); Ovulation Induction; Polymorphism, Genetic; Pregnancy; Pregnancy Rate
PubMed: 34032987
DOI: 10.1007/s10815-021-02236-8 -
Combinatorial Chemistry & High... 2023Although many trials have evaluated the use of dehydroepiandrosterone to improve outcomes in poor responders undergoing assisted reproductive technology treatment,... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Although many trials have evaluated the use of dehydroepiandrosterone to improve outcomes in poor responders undergoing assisted reproductive technology treatment, evidence supporting this approach is controversial. We aimed to conduct a systematic review and meta-analysis of existing published data to further elucidate and supplement the use of Dehydroepiandrosterone (DHEA) to improve the effectiveness of vitro fertilization in patients with diminished ovarian reserve or adverse ovarian reactions.
METHODS
PubMed, Embase, Cochrane Library, and the Web of Science databases were searched through December 2020. Oocyte yield, metaphase II oocytes, fertilized oocytes, top-quality embryos, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were analyzed as relative outcomes. Meta-analysis was performed and fitted to both fixed-effects models and random-effects models.
RESULTS
Eight prospective randomized controlled studies, five prospective case-control studies, and three retrospective cohort studies were conducted with a total of 1998 participants. Meta-analyses of these studies showed a significantly higher number of oocytes retrieved (WMD 1.09, 95% CI 0.38 to 1.80), metaphase II oocytes (WMD 0.78, 95% CI 0.16 to 1.40), fertilized oocytes (WMD 0.84, 95% CI 0.42 to 1.26), top-quality embryos (WMD 0.60, 95% CI 0.34 to 0.86), clinical pregnancy rate (RR 1.35, 95% CI 1.13 to 1.61), and ongoing pregnancy rate (RR 1.82, 95% CI 1.34 to 2.46), although there was no difference in live birth rate (RR 1.35, 95% CI 0.94 to 1.94) in the DHEA supplementation groups compared with that in the control groups.
CONCLUSION
Oral DHEA supplementation appears to improve some IVF outcomes. On the basis of this limited evidence, we conclude that further studies are required to provide sufficient data.
Topics: Pregnancy; Female; Humans; Dehydroepiandrosterone; Retrospective Studies; Fertilization in Vitro; Pregnancy Rate; Ovary
PubMed: 35996249
DOI: 10.2174/1386207325666220820164357 -
Reproductive Biomedicine Online Jun 2020This systematic review and meta-analysis of comparative studies investigated whether progestins are as effective as gonadotrophin releasing hormone (GnRH) analogues for... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis of comparative studies investigated whether progestins are as effective as gonadotrophin releasing hormone (GnRH) analogues for pituitary suppression in assisted reproduction. The primary outcome was live birth rate per woman. Secondary outcomes were live birth or ongoing pregnancy per woman and per embryo transfer, ongoing pregnancy, clinical pregnancy, numbers of oocytes and metaphase-two oocytes, duration of stimulation and gonadotrophin consumption. Adverse events included miscarriage, ectopic pregnancy and multiple pregnancy rates. The GRADE system was used to assess the quality of evidence. Seven studies involving a total of 2047 women were included. Three studies compared a progestin with a GnRH antagonist and four studies compared a progestin with a GnRH agonist. Most studies are non-randomized and report outcomes per embryo transfer, rather than per woman. Although progestins were similar to GnRH antagonists in effectiveness and safety parameters, they were associated with significantly higher live birth or ongoing pregnancy per embryo transfer compared with the short GnRH agonist protocol (RR 1.49, 95% CI 1.16 to 1.91). Progestin primed stimulation lasted significantly longer (mean difference 0.61 days, 95% CI 0.33 to 0.89) and required significantly more gonadotrophins (mean difference 433.2 IU, 95% CI 311.11 to 555.19) than the short GnRH agonist protocol, but the differences were clinically negligible. Safety parameters were similar between progestins and GnRH agonists. In conclusion, progestins can effectively prevent premature ovulation in assisted reproductive technology cycles. If larger and well-designed studies confirm these findings, progestins may be an effective and low-cost alternative to GnRH analogues when a fresh embryo transfer is not planned owing to a medical indication.
Topics: Adult; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovulation Induction; Pregnancy; Progestins
PubMed: 32327297
DOI: 10.1016/j.rbmo.2020.01.027 -
Theriogenology Sep 2022Modulation of phosphoinositide 3-kinase/protein kinase B/phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway in mammals yields mixed results. A deep understanding...
Role of phosphoinositide 3-kinase/ protein kinase B/ phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway inhibitors during in vitro maturation of mammalian oocytes on in vitro embryo production: A systematic review.
Modulation of phosphoinositide 3-kinase/protein kinase B/phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway in mammals yields mixed results. A deep understanding of its regulation can be a powerful tool for better in vitro blastocyst production. This systematic review aims to map the evidence of PI3K/AKT/PTEN pathway modulation during in vitro maturation (IVM), to assess its effects on meiosis resumption and nuclear maturation progression of mammalian oocytes, and their impacts on embryo development and quality. A total of 1058 articles were screened in three databases, and 22 articles were included. Fifty-two IVM assessments were identified, among which 11 evaluated blastocyst yield. Three PI3K inhibitors (3-methyladenine, Wortmannin, and LY294002) and one AKT inhibitor (SH6) were investigated. The impact of this pathway modulation on meiosis resumption in swines and murines was not well established, depending on the inhibitor used, concentration, and media supplementation, while in bovines, resumption seems to be independent of PI3K/AKT/PTEN pathway. However, progression to metaphase II (MII) is highly controlled by this pathway on both bovines and swines. Studies that focused on the inhibition reversibility showed that the removal of the modulator produced MII rates similar to the control group. Experiments that aimed to temporarily block meiosis resumption or reduce PI3K activity resulted in blastocyst production equal to or even higher than control groups. Altogether, these data indicate the paramount potential of this pathway as a possible strategy to improve overall in vitro embryo production efficiency, by synchronizing both nuclear and cytoplasmic maturation.
Topics: Animals; In Vitro Oocyte Maturation Techniques; Mammals; Meiosis; Oocytes; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Phosphoric Monoester Hydrolases; Proto-Oncogene Proteins c-akt; Tensins
PubMed: 35724451
DOI: 10.1016/j.theriogenology.2022.06.009 -
Fertility and Sterility Jul 2020To evaluate the effectiveness of growth hormone (GH) supplementation in improving the in vitro fertilization (IVF) outcomes of poor responders. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effectiveness of growth hormone (GH) supplementation in improving the in vitro fertilization (IVF) outcomes of poor responders.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Poor ovarian responders undergoing conventional IVF or intracytoplasmic sperm injection (ICSI).
INTERVENTION(S)
Randomized controlled trials (RCTs) of poor ovarian responders undergoing a single IVF/ICSI cycle with GH supplementation versus conventional controlled ovarian stimulation. This review was registered in the PROSPERO database before starting data extraction (CRD42020151681).
MAIN OUTCOME MEASURE(S)
Primary outcome was live birth rate. Clinical pregnancy rate, miscarriage rate, ongoing pregnancy rate, number of oocytes, number of mature (metaphase II [MII]) oocytes and the number of embryos available to transfer were considered as secondary outcomes.
RESULT(S)
Twelve RCTs were included; 586 women were assigned to the intervention group and 553 to the control group. The analysis revealed that patients receiving GH supplementation did not show an increased live birth rate, miscarriage rate, or ongoing pregnancy rate. However, GH supplementation in poor responders increased clinical pregnancy rate, number of oocytes retrieved (mean difference 1.62), number of MII oocytes (mean difference 2.06), and number of embryos available to transfer (mean difference 0.76). Sensitivity and subgroup analyses did not provide statistical changes to pooled results.
CONCLUSION(S)
The present meta-analysis provides evidence that GH supplementation may improve some reproductive outcomes in poor responders, but not live birth rates.
Topics: Birth Rate; Drug Resistance; Drug Therapy, Combination; Female; Fertility Agents, Female; Fertilization in Vitro; Growth Hormone; Humans; Infant, Newborn; Infertility; Live Birth; Male; Oocyte Retrieval; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic; Treatment Outcome
PubMed: 32553470
DOI: 10.1016/j.fertnstert.2020.03.007 -
Reproductive Biomedicine Online Feb 2023Does flushing of the follicles at ovum retrieval increase the number of retrieved oocytes in poor-response IVF patients? (Meta-Analysis)
Meta-Analysis
RESEARCH QUESTION
Does flushing of the follicles at ovum retrieval increase the number of retrieved oocytes in poor-response IVF patients?
DESIGN
An update of an electronic literature search was performed to identify randomized controlled trials (RCT) investigating follicular flushing versus no flushing in women with a poor response to IVF treatment. No exclusion criteria for type of needle, stimulation or protocol were applied. A meta-analysis was conducted using the software RevMan 5.4.
RESULTS
Six RCT were identified that had the primary objective of testing for an increase in mean number of cumulus-oocyte complexes or/and metaphase II oocytes between flushing and no flushing. A double-lumen needle was used in five trials, one study investigated a pseudo-double-lumen needle, and a conventional single-lumen needle was used in all the control groups. The main risk of bias in all the included studies is a lack of blinding of the physicians performing the puncture and incomplete data in four trials. A heterogeneity of direction and size of effect of follicular flushing on mean oocyte number retrieved was detected (I = 80, P = 0.0001), which precludes a synthesis of the data. Two studies showed a decrease or tendency towards a decrease in oocyte numbers, one study showed similar oocyte numbers, and one study showed a strong tendency towards increased oocyte numbers with flushing. A similar picture was seen for metaphase II oocytes (I = 73, P = 0.002).
CONCLUSIONS
It is uncertain whether follicular flushing in poor-response IVF patients affects the number of retrieved oocytes. Larger pragmatic trials are warranted to clarify the effect of flushing on oocyte numbers and clinical outcomes in poor responders and monofollicular patients.
Topics: Female; Humans; Pregnancy; Embryo Transfer; Fertilization in Vitro; Oocyte Retrieval; Oocytes; Ovulation Induction; Pregnancy Rate; Randomized Controlled Trials as Topic
PubMed: 36566145
DOI: 10.1016/j.rbmo.2022.11.011 -
Journal of Ovarian Research Sep 2020Previous studies have investigated the effects of anti-Müllerian hormone (AMH) and AMH type II receptor (AMHR2) polymorphisms on ovarian stimulation outcomes, but the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have investigated the effects of anti-Müllerian hormone (AMH) and AMH type II receptor (AMHR2) polymorphisms on ovarian stimulation outcomes, but the results were inconsistent.
METHODS
We searched PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases for the literature used in this meta-analysis. The meta-analysis was performed with a random effects model with RevMan 5.3.5. Results were expressed as the relative risk (RR) for discrete data and the mean difference (MD) for continuous outcomes with a 95% confidence interval (CI).
RESULTS
Seven studies with 2078 participants were included. More metaphase II (MII) oocytes were retrieved in the T allele carrier of AMH (rs10407022) in the dominant model (MD: 1.20, 95% CI: 0.76 to 1.65, I = 0%, P < 0.00001), homozygote model (MD: 1.68, 95% CI: 0.35 to 3.01, I = 70%, P = 0.01) and heterogeneity model (MD: 1.20, 95% CI: 0.74 to 1.66, I = 0%, P < 0.00001). Oocytes retrieved from the Asian region in the TT carrier were significantly lesser than those in the GG/GT carrier in AMH (rs10407022) (MD: -1.41, 95% CI: - 1.75 to - 1.07, I = 0%). Differences in the stimulation duration, gonadotropin (Gn) dosage, and pregnancy rate were insignificant.
CONCLUSIONS
Our analysis indicated that the polymorphisms of AMH/AMHR2 could influence the ovarian stimulation outcomes. Prospective studies with a larger sample size and more rigorous design are needed in the future to further confirm these findings.
Topics: Female; Humans; Pregnancy; Anti-Mullerian Hormone; Follicle Stimulating Hormone; Ovulation Induction; Polymorphism, Genetic; Pregnancy Rate; Prospective Studies; Receptors, Peptide; Receptors, Transforming Growth Factor beta
PubMed: 32887648
DOI: 10.1186/s13048-020-00699-4 -
Acta Obstetricia Et Gynecologica... Oct 2019High levels of anti-Mullerian hormone and a high antral follicle count in women with polycystic ovary syndrome, reflecting increased ovarian antral follicles,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
High levels of anti-Mullerian hormone and a high antral follicle count in women with polycystic ovary syndrome, reflecting increased ovarian antral follicles, predisposes them to have a high number of retrieved oocytes with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and an increased risk of ovarian hyperstimulation syndrome. Inositols, which act as insulin sensitizers, have the potential to alter folliculogenesis and the functional ovarian reserve, with subsequent benefits to reproductive outcomes following IVF/ICSI treatment. Published literature is, however, unable to provide definitive evidence of its efficacy. The objective of our review was to evaluate the effect of inositols on anti-Mullerian hormone, antral follicle count and reproductive outcomes in women with polycystic ovary syndrome undergoing IVF/ICSI.
MATERIAL AND METHODS
We performed a literature search using standard methodology recommended by Cochrane. Randomized controlled trials and non-randomized studies comparing inositols with no treatment, placebo or other treatment were included in the review. Using standard methodology recommended by Cochrane we pooled results using the random effects model; our findings were reported as relative risk or mean differences. PROSPERO registration: CRD42017082275.
RESULTS
We included 18 trials. The primary outcome was a change in anti-Mullerian hormone and antral follicle count before and after treatment, for which data were unsuitable for meta-analysis. A narrative review showed no consistent direction or size of effect. A meta-analysis for the secondary outcomes showed no evidence of a significant difference between inositol and control groups for any outcome: number of oocytes (mean difference -0.39, 95% confidence interval [CI] -1.11 to 0.33), number of metaphase II oocytes (mean difference 0.29, 95% CI -0.83 to 1.40), number of top grade embryos (risk ratio [RR] 1.02, 95% CI 0.93-1.12), clinical pregnancy rate (RR 1.16, 95% CI 0.87-1.53), and risk of ovarian hyperstimulation syndrome (RR 0.73, 95% CI 0.39-1.37). The quality of evidence was assessed as very low.
CONCLUSIONS
There is insufficient evidence for an effect of inositols on ovarian reserve markers and to support their use as pretreatment before IVF/ICSI in women with polycystic ovary syndrome.
Topics: Anti-Mullerian Hormone; Female; Fertilization in Vitro; Humans; Inositol; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovarian Reserve; Polycystic Ovary Syndrome; Sperm Injections, Intracytoplasmic
PubMed: 30993683
DOI: 10.1111/aogs.13625 -
Reproductive Biomedicine Online Apr 2024This systematic review and meta-analysis aimed to evaluate the impact of ovarian endometriomas (OMA) on indirect markers of oocyte quality in patients undergoing IVF,... (Review)
Review
This systematic review and meta-analysis aimed to evaluate the impact of ovarian endometriomas (OMA) on indirect markers of oocyte quality in patients undergoing IVF, compared with women without anatomical or functional ovarian abnormalities. The search spanned original randomized controlled trials, case-control studies and cohort studies published in MEDLINE, the Cochrane Controlled Trials Register and the ClinicalTrials.gov database up to October 2023. Thirty-one studies were included in the meta-analysis, showing no significant differences in fertilization (OR 1.10, 95% CI 0.94-1.30), blastulation (OR 0.86, 95% CI 0.64-1.14) and cancellation (OR 1.06, 95% CI 0.78-1.44) rates. However, patients with OMA exhibited significantly lower numbers of total and mature (metaphase II) oocytes retrieved (mean difference -1.59, 95% CI -2.25 to -0.94; mean difference -1.86, 95% CI -2.46 to -1.26, respectively), and lower numbers of top-quality embryos (mean difference -0.49, 95% CI -0.92 to -0.06). The Ovarian Sensitivity Index was similar between the groups (mean difference -1.55, 95% CI -3.27 to 0.18). The lack of data published to date prevented meta-analysis on euploidy rate. In conclusion, although the presence of OMA could decrease the oocyte yield in patients undergoing IVF/intracytoplasmic sperm injection, it does not appear to have an adverse impact on oocyte quality.
PubMed: 38943812
DOI: 10.1016/j.rbmo.2024.104075