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Reproductive Biomedicine Online Dec 2023The aim of this systematic review and meta-analysis was to quantify the effect of random start ovarian stimulation (RSOS) compared with conventional start ovarian... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review and meta-analysis was to quantify the effect of random start ovarian stimulation (RSOS) compared with conventional start ovarian stimulation (CSOS) in cancer patients before gonadotoxic treatment. The final analytical cohort encompassed 688 RSOS and 1076 CSOS cycles of cancer patients before gonadotoxic treatment. Eleven studies were identified by database searches of MEDLINE, Cochrane Library and cited references. The primary outcomes of interest were the number of oocytes and mature oocytes collected, the number of embryos cryopreserved and the metaphase II (MII)-antral follicle count (AFC) ratio. The studies were rated from medium to high quality (from 6 to 9) according to the Newcastle-Ottawa Quality Assessment Scale. The two protocols resulted in similar numbers of oocytes collected, MII oocytes, embryos available for cryopreservation and comparable MII-AFC and fertilization rates. The duration of ovarian stimulation was longer (standardized mean difference [SMD] 0.35, 95% CI 0.09 to 0.61; P = 0.009) and gonadotrophin consumption was higher (SMD 0.23, 95% CI 0.06 to 0.40; P = 0.009) in RSOS compared with CSOS. This systematic review and meta-analysis show that the duration of stimulation is longer, and the total gonadotrophin consumption is higher in cancer patients undergoing RSOS compared with those undergoing CSOS, with no significant effect on mature oocyte yield.
Topics: Humans; Female; Fertility Preservation; Oocyte Retrieval; Cryopreservation; Neoplasms; Oocytes; Gonadotropins; Ovulation Induction; Retrospective Studies
PubMed: 37857156
DOI: 10.1016/j.rbmo.2023.103337 -
European Journal of Obstetrics,... Oct 2023To conduct a systematic review andmeta-analysis of all randomized controlled trials (RCTs) that investigated whether dual triggering [a combination of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a systematic review andmeta-analysis of all randomized controlled trials (RCTs) that investigated whether dual triggering [a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG)] of final oocyte maturation can improve the number of oocytes retrieved and clinical pregnancy rate in low or normal responders undergoing in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles using a GnRH-antagonist protocol.
STUDY DESIGN
Studies up to October 2022 were identified from PubMed, Scopus, Cochrane Library and Web of Science. The risk of bias of included studies was assessed. Dichotomous outcomes were reported as relative risks (RR), and continuous outcomes were reported as weighted mean differences (WMD) with 95% confidence intervals (CI). The primary outcomes were number of oocytes retrieved, number of mature [metaphase II (MII)] oocytes, clinical pregnancy rate and ongoing pregnancy rate; other IVF outcomes were considered as secondary outcomes.
RESULTS
Seven studies were identified, and 898 patients were eligible for inclusion in this meta-analysis. The results showed that the number of oocytes retrieved [WMD = 1.38 (95% CI 0.47-2.28), I = 66%, p = 0.003, low evidence], number of MII oocytes [WMD = 0.7 (95% CI 0.35-1.05), I = 42%, p < 0.0001, moderate evidence], number of embryos [WMD = 0.68 (95% CI 0.07-1.3), I = 67%, p = 0.03, low evidence] and number of good-quality embryos [WMD = 1.14 (95% CI 0.35-1.93), I = 0%, p = 0.005, moderate evidence] in the dual trigger group were significantly higher than in the hCG trigger group. The results of the ovarian response subgroup analysis showed significant differences in all of these outcomes in normal responders, and no differences in any of the outcomes in low responders, except for the number of MII oocytes. In low responders, clinical pregnancy rates may be improved in the dual trigger group [RR = 2.2 (95% CI 1.05-4.61), I = 28%, p = 0.04, low evidence].
CONCLUSION
Dual triggering by GnRH agonist and hCG improved oocyte maturity and embryo grading for normal responders in GnRH-antagonist cycles. Dual triggering for final oocyte maturation may improve clinical pregnancy rates in low responders.
Topics: Female; Pregnancy; Humans; Sperm Injections, Intracytoplasmic; Randomized Controlled Trials as Topic; Ovulation; Fertilization in Vitro; Chorionic Gonadotropin; Hormone Antagonists; Gonadotropin-Releasing Hormone
PubMed: 37639817
DOI: 10.1016/j.ejogrb.2023.08.014 -
Frontiers in Endocrinology 2023Polycystic ovary syndrome (PCOS) is a common endocrinopathy causing infertility in childbearing women. Progestin-primed ovarian stimulation (PPOS) protocol has recently... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Polycystic ovary syndrome (PCOS) is a common endocrinopathy causing infertility in childbearing women. Progestin-primed ovarian stimulation (PPOS) protocol has recently been used for infertile women. However, whether PPOS provides a significant benefit over gonadotropin-releasing hormone (GnRH) analogue protocols in PCOS is still controversial. The objective of this systematic review is to investigate the efficacy of PPOS in patients with PCOS during fertilization (IVF) or intracytoplasmic sperm injection (ICSI). We searched Medline, Embase, Google Scholar, ClinicalTrials, and Cochrane Central Register of Controlled Trials from inception to April 1, 2023. Randomized controlled trials (RCTs) and observational studies comparing the efficacy between PPOS and conventional GnRH analogue protocols in patients with PCOS in English were included. The primary outcomes included live birth rate, the incidence of moderate or severe ovarian hyperstimulation syndrome (OHSS), and the number of metaphase II oocytes. The pooled estimates were calculated using the random-effects models as odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CIs). Three RCTs and six cohort studies involving 2289 patients were included. Results from RCTs suggest that PPOS leads to no significant difference in the risk of OHSS, the number of metaphase II oocytes, or the rate of live birth when compared to GnRH analogue protocols. The pooling estimates of cohort studies showed consistent results. Additionally, in cohort studies, PPOS required a higher dose of Gn and tended to improve the implantation rate, clinical pregnancy rate, and ongoing pregnancy rate. For subgroup analyses, the higher implantation rate, clinical pregnancy rate, and ongoing pregnancy rate were found in PPOS compared to the GnRH agonist short protocol. However, the certainty of the evidence for the outcomes was generally low. Overall, There is currently no evidence to support that PPOS could reduce the risk of OHSS, increase oocyte maturation, or improve pregnancy outcomes in women with PCOS undergoing IVF/ICSI when compared to GnRH analogue protocols. Considering its efficiency and safety, this protocol could be a patient-friendly and viable alternative for PCOS patients, especially when frozen-thawed embryo transfer is planned. Future high-quality randomized trials with children's long-term safety and cost-effective analyses are still required.
SYSTEM REVIEW REGISTRATION
NPLASY (202340059). https://inplasy.com/inplasy-2023-4-0059/.
Topics: Female; Humans; Pregnancy; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Progestins; Steroids
PubMed: 37795363
DOI: 10.3389/fendo.2023.1224858 -
Reproductive Biomedicine Online Jul 2015In this systematic review and meta-analysis, the effect of ovarian endometrioma on ovarian responsiveness to stimulation and on assisted reproduction outcomes was... (Meta-Analysis)
Meta-Analysis Review
In this systematic review and meta-analysis, the effect of ovarian endometrioma on ovarian responsiveness to stimulation and on assisted reproduction outcomes was evaluated. Nine published studies (1039 cases) were included. The number of oocytes retrieved (mean difference [MD] -1.50; 95% CI, -2.84 to -0.15, P = 0.03), metaphase II (MII) oocytes retrieved (MD -3.61; 95% CI -4.44 to -2.78, P < 0.00001) and total embryos formed (MD -0.66; 95% CI -1.13 to -0.18, P = 0.007) were significantly lower in women with ovarian endometrioma than the control group. Gonadotrophin dose, duration of stimulation, number of good-quality embryos, implantation rate, clinical pregnancy rate and live birth rate were similar. Comparisons between ovaries with endometriomas and healthy ovaries of the same individuals were also made. Number of oocytes retrieved, MII oocytes retrieved and total embryos formed were not statistically significantly different between the affected ovaries and contralateral normal ovaries. Observational studies showed that ovarian endometrioma was associated with fewer oocytes retrieved, fewer MII oocytes retrieved and fewer total formed embryos. Clinical pregnancy rate and live birth rates were not affected. Intra-patient comparisons in women with unilateral endometrioma suggested the number of oocytes retrieved, MII oocytes retrieved and total embryos formed were similar.
Topics: Birth Rate; Embryo Implantation; Endometriosis; Female; Fertilization in Vitro; Humans; Ovarian Diseases; Ovary; Ovulation Induction; Pregnancy; Pregnancy Rate; Time Factors; Treatment Outcome
PubMed: 25982092
DOI: 10.1016/j.rbmo.2015.03.005 -
Reproductive Biomedicine Online Apr 2018A systematic literature review and meta-analysis was conducted to evaluate the effect of follicular flushing on clinical outcomes (primary outcome: mean number of... (Review)
Review
A systematic literature review and meta-analysis was conducted to evaluate the effect of follicular flushing on clinical outcomes (primary outcome: mean number of cumulus-oocyte-complexes [COC]) in poor-response IVF patients). The bibliographic databases OvidMedline (includes Pubmed), Cochrane Library and Web of Science were searched electronically for randomized controlled trials (RCT) comparing follicular flushing with no flushing. Three RCT with a total of 210 patients could be included. The mean number of COC did not increase with flushing (weighted mean difference: -0.45 COC, 95% CI -1.14 to 0.25, I = 70%; P = 0.21; three RCT, n = 210). Mean number of metaphase II oocytes and the proportion of randomized patients having at least one COC retrieved were no different between groups. No difference was observed between groups for mean number of embryos, the proportion of randomized patients achieving embryo transfer, clinical pregnancy and live birth rates. Procedure duration was significantly increased with flushing (P = 0.0006). A positive effect of flushing on any of the investigated outcomes could not be observed in the existing literature in patients with poor ovarian response. Flushing is unlikely to significantly increase the number of oocytes, and the routine use of follicular flushing should, therefore, be scrutinized.
Topics: Embryo Transfer; Female; Fertilization in Vitro; Humans; Oocyte Retrieval; Ovulation Induction; Pregnancy; Treatment Outcome
PubMed: 29336996
DOI: 10.1016/j.rbmo.2017.12.014 -
Fertility and Sterility Apr 2021To determine whether follicle flushing during oocyte retrieval improves live birth or secondary outcomes in assisted reproductive technology (ART). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine whether follicle flushing during oocyte retrieval improves live birth or secondary outcomes in assisted reproductive technology (ART).
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Women undergoing ART using autologous gametes.
INTERVENTION(S)
A systematic search of PubMed, EMBASE, Cochrane Database, and Web of Science for randomized controlled trials comparing follicle flushing to direct aspiration during oocyte retrieval published in English between 1989 to 2020.
MAIN OUTCOME MEASURE(S)
Live birth as primary outcome, and clinical and ongoing pregnancy, total and mature metaphase II (MII) oocytes retrieved, and operating time as secondary outcomes.
RESULT(S)
Eleven studies were included totaling 1,178 cases. No difference in live birth was demonstrated between follicle flushing and direct aspiration. Clinical pregnancy and ongoing pregnancy were not improved with flushing. Total oocyte and MII yield were lower with flushing compared with direct aspiration. Procedure time was increased with flushing by 2 minutes in poor responders and 9 minutes in normal responders. Other sensitivity analyses did not demonstrate any changes, except the difference in MII yield was no longer statistically significant.
CONCLUSION(S)
Follicle flushing during oocyte retrieval increases procedure time and does not improve live birth or secondary ART outcomes. Randomized data do not support the use of follicle flushing as an intervention in ART.
Topics: Adult; Female; Humans; Live Birth; Oocyte Retrieval; Operative Time; Ovarian Follicle; Ovulation Induction; Pregnancy; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted
PubMed: 33676753
DOI: 10.1016/j.fertnstert.2020.10.064 -
Reproductive Biomedicine Online Jan 2023A systematic review and meta-analysis was performed aiming to identify good-quality randomized controlled trials (RCT) evaluating testosterone pretreatment in poor... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis was performed aiming to identify good-quality randomized controlled trials (RCT) evaluating testosterone pretreatment in poor responders. Eight RCTs were analysed, evaluating 797 women. Transdermal testosterone gel was used in all studies, with a dose ranging from 10 to 12.5 mg/day for 10-56 days. The main outcome measure was achievement of pregnancy, expressed as clinical pregnancy or live birth. Testosterone pretreatment was associated with a significantly higher live birth (risk ratio [RR] 2.07, 95% confidence interval [CI] 1.09-3.92) and clinical pregnancy rate (RR 2.25, 95% CI 1.54-3.30), as well as a significant increase in the number of cumulus-oocyte complexes retrieved. Significantly fewer days to complete ovarian stimulation, a lower total dose of gonadotrophins, a lower cancellation rate due to poor ovarian response and a thicker endometrium on the day of triggering of final oocyte maturation were observed. No significant differences were observed in oestradiol concentration, the numbers of follicles ≥17 mm, metaphase II oocytes, two-pronuclear oocytes and embryos transferred, and the proportion of patients with embryo transfer. The current study suggests that the probability of pregnancy is increased in poor responders pretreated with transdermal testosterone who are undergoing ovarian stimulation for IVF.
Topics: Pregnancy; Female; Humans; Testosterone; Birth Rate; Fertilization in Vitro; Pregnancy Rate; Ovulation Induction; Live Birth
PubMed: 36369150
DOI: 10.1016/j.rbmo.2022.09.022 -
Frontiers in Oncology 2020The co-administration of letrozole during controlled ovarian stimulation (COS) with gonadotropins is used to limit the potentially harmful effects of a...
The co-administration of letrozole during controlled ovarian stimulation (COS) with gonadotropins is used to limit the potentially harmful effects of a supra-physiological rise in estrogen levels on hormone-sensitive cancers. However, the efficacy and safety of adding letrozole to COS remain debated. This is a systematic review and meta-analysis of published studies that compared the efficacy and safety of COS with co-administration of letrozole vs. COS without letrozole in all patient populations. A secondary analysis was done including only the studies in breast cancer patients. The primary efficacy endpoint was the number of retrieved mature Metaphase II (MII) oocytes. Secondary efficacy and safety endpoints were total number of oocytes, maturation rate, fertilization rate, number of cryopreserved embryos, peak estradiol levels, progesterone levels, and total gonadotropin dose. Data for each endpoint were reported and analyzed thorough mean ratio (MR) with 95% confidence interval (CI). A total of 11 records were selected including 2,121 patients (990 patients underwent COS with letrozole and 1,131 COS without letrozole). The addition of letrozole to COS did not have any negative effect on the number of mature oocytes collected (MR = 1.00, 95% CI = 0.87-1.16; = 0.967) and the other efficacy endpoints. COS with letrozole was associated with significantly decreased peak estradiol levels (MR = 0.28, 95% CI = 0.24-0.32; < 0.001). Similar results were observed in the secondary analysis including only breast cancer patients. These findings are reassuring on the efficacy and safety of COS with gonadotropins and letrozole and are particularly important for fertility preservation in women with hormone-sensitive cancers.
PubMed: 33117711
DOI: 10.3389/fonc.2020.574669 -
Human Reproduction Update Sep 2018Genotype has been implicated in the outcome of ovarian stimulation. The analysis of patient-specific genotypes might lead to an individualized pharmacogenomic approach... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Genotype has been implicated in the outcome of ovarian stimulation. The analysis of patient-specific genotypes might lead to an individualized pharmacogenomic approach to controlled ovarian stimulation (COS). However, the validity of such an approach remains to be established.
OBJECTIVE AND RATIONALE
To define the impact of specific genotype profiles of follicle-stimulating hormone, luteinizing hormone and their receptors (FSHR, LHR and LHCGR) on ovarian stimulation outcome. Specifically, our aim was to identify polymorphisms that could be useful in clinical practice, and those that need further clinical investigation.
SEARCH METHODS
A systematic review followed by a meta-analysis was performed according to the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines without time restriction. We searched the PubMed/MEDLINE, Cochrane Library, SCOPUS and EMBASE databases to identify all relevant studies published before January 2017. Only clinical trials published as full-text articles in peer-reviewed journals were included. The primary outcome was the number of oocytes retrieved.
OUTCOMES
Fifty-seven studies were assessed for eligibility, 33 of which were included in the qualitative and quantitative analyses. Data were independently extracted using quality indicators. COS outcomes related to seven polymorphisms (FSHR [rs6165], FSHR [rs6166], FSHR [rs1394205], LHB [rs1800447], LHB [rs1056917], LHCGR [rs2293275] and LHCGR [rs13405728]) were evaluated. More oocytes were retrieved from FSHR (rs6165) AA homozygotes (five studies, 677 patients, weighted mean difference [WMD]: 1.85, 95% CI: 0.85-2.85, P < 0.001; I2 = 0%) than from GG homozygotes and AG heterozygotes (four studies, 630 patients, WMD: 1.62, 95% CI: 0.28-2.95, P = 0.020; I2 = 56%). Moreover, stimulation duration was shorter in FSHR (rs6165) AA homozygotes than in AG carriers (three studies, 588 patients, WMD -0.48, 95% CI: -0.87 to -0.10, P = 0.010, I2 = 44%). A higher number of oocytes (21 studies, 2632 patients WMD: 0.84, 95% CI: 0.19 to 1.49, P = 0.01, I2 = 76%) and metaphase II oocytes (five studies, 608 patients, WMD: 1.03, 95% CI: 0.01-2.05, P = 0.050, I2 = 0%) was observed in AA than in GG homozygote carriers. FSH consumption was significantly lower in FSHR (rs1394205) GG homozygotes (three studies, 411 patients, WMD: -1294.61 IU, 95% CI: -593.08 to -1996.14 IU, P = 0.0003, I2 = 99%) and AG heterozygotes (three studies, 367 patients, WMD: -1014.36 IU, 95% CI: -364.11 to -1664.61 IU, P = 0.002, I2 = 99%) than in AA homozygotes.
WIDER IMPLICATIONS
These results support the clinical relevance of specific genotype profiles on reproductive outcome. Further studies are required to determine their application in a pharmacogenomic approach to ovarian stimulation.
Topics: Female; Follicle Stimulating Hormone; Genotype; Gonadotropins; Humans; Luteinizing Hormone; Ovulation Induction; Pharmacogenomic Variants; Receptors, FSH; Receptors, LH
PubMed: 29924306
DOI: 10.1093/humupd/dmy019 -
Gynecological Endocrinology : the... Apr 2013The results of several studies about the effectiveness of recombinant luteinizing hormone (rLH) supplementation in poor responder in vitro fertilization (IVF) patients... (Meta-Analysis)
Meta-Analysis Review
The results of several studies about the effectiveness of recombinant luteinizing hormone (rLH) supplementation in poor responder in vitro fertilization (IVF) patients were conflicting. To evaluate the current available data regarding the efficacy of rLH supplementation in poor responders, a meta-analysis was performed. A systemic search was performed without language limitation but restricted to randomized controlled trial (RCT). We mainly explored MEDLINE, EMBASE, CNKI and Cochrane Library for the relevant studies. Three studies were considered eligible for inclusion. The meta-analysis indicated that rLH supplementation did not increase the ongoing pregnancy rate in poor responders (OR 1.30, 95% CI: 0.80, 2.11). Furthermore, there was no significant difference in the number of oocytes retrieved, total dose of rFSH used, total duration of stimulation, number of retrieved metaphase II oocytes and cycle cancellation rate between the study and control groups. In conclusions, the available evidence does not support the addition of rLH in poor responders treated with rFSH and GnRHa for IVF. It was inconclusive. Future research should be based on strict criteria to define poor responders, and large, well-designed RCTs are necessary to definitively answer the important question of whether there was need to use rLH in poor responders undergoing IVF.
Topics: Female; Fertilization in Vitro; Humans; Luteinizing Hormone; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins; Treatment Outcome
PubMed: 23347045
DOI: 10.3109/09513590.2012.743016