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Journal of Gynecology Obstetrics and... Sep 2021To systematically evaluate the effect of progestin-primed ovarian stimulation (PPOS) in in vitro fertilization (IVF)/oocyte intracytoplasmic sperm injection-embryo... (Meta-Analysis)
Meta-Analysis
PURPOSE
To systematically evaluate the effect of progestin-primed ovarian stimulation (PPOS) in in vitro fertilization (IVF)/oocyte intracytoplasmic sperm injection-embryo transfer (ICSI-ET) in patients with poor ovarian response and to find an optimal ovulation induction protocol for such patients.
METHOD
A literature search of PubMed, Medline, EBSCO, Cochrane Library, Vip.com, CNKI, and the Wanfang database was conducted to find case-control studies of PPOS with medroxyprogesterone acetate and other traditional stimulation regimens for ovulation induction in patients with poor ovarian response. The period of time searched was from the database establishment to August 2020. Patients in the experimental group underwent PPOS and those in the control group underwent another program (e.g., the gonadotropin-releasing hormone antagonist protocol). RevMan 5.3 software was used for meta-analysis.
RESULTS
A total of sixteen case-control studies (one of them is randomized controlled trial), with 4422 induction cycles, were included. All the included patients met the 2011 Bologna diagnostic criteria for poor ovarian response. The numbers of mature eggs, available embryos, optimal embryos, and the rate of cumulative pregnancies in the PPOS group were all better than those in the control group (P<0.05). There was a lower Serum luteinizing hormone on the day of human chorionic gonadotropin (HCG) injection and a lower rate of cycle cancellation in the PPOS group (P<0.05). No other differences between PPOS and other treatments were statistically significant.
CONCLUSION
PPOS can reduce the need for cycle cancellation, improve the follicles and embryos, and improve the pregnancy rate and thus, can present an effective choice for IVF/ICSI-ET in patients with poor ovarian response.
Topics: Adult; Case-Control Studies; Contraceptive Agents, Hormonal; Female; Humans; Medroxyprogesterone Acetate; Ovary; Ovulation Induction; Treatment Outcome
PubMed: 33387677
DOI: 10.1016/j.jogoh.2020.102049 -
Cancer Chemotherapy and Pharmacology Jan 2021Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small.
METHODS
To determine the effects of HSD3B1 (1245C) variant on resistance to androgen-deprivation therapy in prostate cancer, we performed a meta-analysis of the available literature. Electronic database searches identified appropriately designed studies that detected HSD3B1 in prostate cancer. We conducted a systematic search of studies in the following databases: PubMed, and EMBASE published until August 10, 2020 using the following search terms: (HSD3B1 AND ((((prostate cancer) OR prostatic neoplasm) OR prostatic carcinoma) OR prostatic cancer).
RESULTS
Eight researches were included in this research. The result validated that the HSD3B1 (1245C) variant allele was associated with a shorter PFS (HR, 1.97; 95% CI, 1.39-2.79; P = 0.0001) (homozygous wild-type group) in men with prostate cancer when treated with ADT, however, a higher PFS (HR, 0.68; 95% CI, 0.48-0.96; P = 0.03) when treated with ADT and CYP17A1 inhibitor.
CONCLUSION
The HSD3B1 (1245C) variant is a predictor of ADT plus CYP17A1 inhibitor response in prostate cancer.
Topics: Alleles; Androgen Antagonists; Drug Resistance, Neoplasm; Humans; Male; Multienzyme Complexes; Mutation; Progesterone Reductase; Prostatic Neoplasms; Steroid 17-alpha-Hydroxylase; Steroid Isomerases; Treatment Outcome
PubMed: 33141329
DOI: 10.1007/s00280-020-04192-z -
The Cochrane Database of Systematic... Oct 2020A frozen embryo transfer (FET) cycle is when one or more embryos (frozen during a previous treatment cycle) are thawed and transferred to the uterus. Some women undergo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A frozen embryo transfer (FET) cycle is when one or more embryos (frozen during a previous treatment cycle) are thawed and transferred to the uterus. Some women undergo fresh embryo transfer (ET) cycles with embryos derived from donated oocytes. In both situations, the endometrium is primed with oestrogen and progestogen in different doses and routes of administration.
OBJECTIVES
To evaluate the most effective endometrial preparation for women undergoing transfer with frozen embryos or embryos from donor oocytes with regard to the subsequent live birth rate (LBR).
SEARCH METHODS
The Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, LILACS, trials registers and abstracts of reproductive societies' meetings were searched in June 2020 together with reference checking and contact with study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. We analysed all available interventions versus placebo, no treatment, or between each other. The primary review outcome was live birth rate. Secondary outcomes were clinical and multiple pregnancy, miscarriage, cycle cancellation, endometrial thickness and adverse effects.
MAIN RESULTS
Thirty-one RCTs (5426 women) were included. Evidence was moderate to very low-quality: the main limitations were serious risk of bias due to poor reporting of methods, and serious imprecision. Stimulated versus programmed cycle We are uncertain whether a letrozole-stimulated cycle compared to a programmed cycle, for endometrial preparation, improves LBR (odds ratio (OR) 1.26, 95% confidence interval (CI) 0.49 to 3.26; 100 participants; one study; very low-quality evidence). Stimulating with follicle stimulating hormone (FSH), letrozole or clomiphene citrate may improve clinical pregnancy rate (CPR) (OR 1.63, 95% CI 1.12 to 2.38; 656 participants; five studies; I = 11%; low-quality evidence). We are uncertain if they reduce miscarriage rate (MR) (OR 0.79, 95% CI 0.36 to 1.71; 355 participants; three studies; I = 0%; very low-quality evidence). Endometrial thickness (ET) may be reduced with clomiphene citrate (mean difference(MD) -1.04, 95% CI -1.59 to -0.49; 92 participants; one study; low-quality evidence). Other outcomes were not reported. Natural versus programmed cycle We are uncertain of the effect from a natural versus programmed cycle for LBR (OR 0.97, 95% CI 0.74 to 1.28; 1285 participants; four studies; I = 0%; very low-quality evidence) and CPR (OR 0.79, 95% CI 0.62 to 1.01; 1249 participants; five studies; I = 60%; very low-quality evidence), while a natural cycle probably reduces the cycle cancellation rate (CCR) (OR 0.60, 95% CI 0.44 to 0.82; 734 participants; one study; moderate-quality evidence). We are uncertain of the effect on MR and ET. No study reported other outcomes. Transdermal versus oral oestrogens From low-quality evidence we are uncertain of the effect transdermal compared to oral oestrogens has on CPR (OR 0.86, 95% CI 0.59 to 1.25; 504 participants; three studies; I = 58%) or MR (OR 0.55, 95% CI 0.27 to 1.09; 414 participants; two studies; I = 0%). Other outcomes were not reported. Day of starting administration of progestogen When doing a fresh ET using donated oocytes in a synchronised cycle starting progestogen on the day of oocyte pick-up (OPU) or the day after OPU, in comparison with recipients that start progestogen the day prior to OPU, probably increases the CPR (OR 1.87, 95% CI 1.13 to 3.08; 282 participants; one study, moderate-quality evidence). We are uncertain of the effect on multiple pregnancy rate (MPR) or MR. It probably reduces the CCR (OR 0.28, 95% CI 0.11 to 0.74; 282 participants; one study; moderate-quality evidence). No study reported other outcomes. Gonadotropin-releasing hormone (GnRH) agonist versus control A cycle with GnRH agonist compared to without may improve LBR (OR 2.62, 95% CI 1.19 to 5.78; 234 participants; one study; low-quality evidence). From low-quality evidence we are uncertain of the effect on CPR (OR 1.08, 95% CI 0.82 to 1.43; 1289 participants; eight studies; I = 20%), MR (OR 0.85, 95% CI 0.36 to 2.00; 828 participants; four studies; I = 0%), CCR (OR 0.49, 95% CI 0.21 to 1.17; 530 participants; two studies; I = 0%) and ET (MD -0.08, 95% CI -0.33 to 0.16; 697 participants; four studies; I = 4%). No study reported other outcomes. Among different GnRH agonists From very low-quality evidence we are uncertain if cycles among different GnRH agonists improves CPR or MR. No study reported other outcomes. GnRH agonists versus GnRH antagonists GnRH antagonists compared to agonists probably improves CPR (OR 0.62, 95% CI 0.42 to 0.90; 473 participants; one study; moderate-quality evidence). We are uncertain of the effect on MR and MPR. No study reported other outcomes. Aspirin versus control From very low-quality evidence we are uncertain whether a cycle with aspirin versus without improves LBR, CPR, or ET. Steroids versus control From very low-quality evidence we are uncertain whether a cycle with steroids compared to without improves LBR, CPR or MR. No study reported other outcomes.
AUTHORS' CONCLUSIONS
There is insufficient evidence on the use of any particular intervention for endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers. In frozen embryo transfers, low-quality evidence showed that clinical pregnancy rates may be improved in a stimulated cycle compared to a programmed one, and we are uncertain of the effect when comparing a programmed cycle to a natural cycle. Cycle cancellation rates are probably reduced in a natural cycle. Although administering a GnRH agonist, compared to without, may improve live birth rates, clinical pregnancy rates will probably be improved in a GnRH antagonist cycle over an agonist cycle. In fresh synchronised oocyte donor cycles, the clinical pregnancy rate is probably improved and cycle cancellation rates are probably reduced when starting progestogen the day of or day after donor oocyte retrieval. Adequately powered studies are needed to evaluate each treatment more accurately.
Topics: Abortion, Spontaneous; Bias; Clomiphene; Cryopreservation; Drug Administration Schedule; Embryo Implantation; Embryo Transfer; Embryo, Mammalian; Endometrium; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Letrozole; Live Birth; Oocyte Donation; Pregnancy; Pregnancy Rate; Progesterone; Progestins; Randomized Controlled Trials as Topic
PubMed: 33112418
DOI: 10.1002/14651858.CD006359.pub3 -
Human Reproduction Update Jan 2021Progestins are capable of suppressing endogenous LH secretion from the pituitary. Progestins can be used orally and are less expensive than GnRH analogues. However,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Progestins are capable of suppressing endogenous LH secretion from the pituitary. Progestins can be used orally and are less expensive than GnRH analogues. However, early endometrial exposure to progestin precludes a fresh embryo transfer (ET), but the advent of vitrification and increasing number of oocyte cryopreservation cycles allow more opportunities for using progestins for pituitary suppression.
OBJECTIVE AND RATIONALE
This review summarizes: the mechanism of pituitary suppression by progestins; the effectiveness of progestins when compared with GnRH analogues and with each other; the effect of progestins on oocyte and embryo developmental potential and euploidy status; and the cost-effectiveness aspects of progestin primed stimulation. Future research priorities are also identified.
SEARCH METHODS
The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, the Web of Science and Scopus were screened with a combination of keywords related to ART, progesterone, GnRH analogue and ovarian stimulation, in various combinations. The search period was from the date of inception of each database until 1 April 2020. Only full text papers published in English were included.
OUTCOMES
Overall, the duration of stimulation, gonadotrophin consumption and oocyte yield were similar with progestins and GnRH analogues. However, sensitivity analyses suggested that progestins were associated with significantly lower gonadotrophin consumption than the long GnRH agonist protocol (mean difference (MD) = -648, 95% CI = -746 to -550 IU) and significantly higher gonadotrophin consumption than the short GnRH agonist protocol (MD = 433, 95% CI = 311 to 555 IU). Overall, live birth, ongoing and clinical pregnancy rates per ET were similar with progestins and GnRH analogues. However, when progestins were compared with GnRH agonists, sensitivity analyses including women with polycystic ovary syndrome (risk ratio (RR) = 1.27, 95% CI = 1.06 to 1.53) and short GnRH agonist protocols (RR = 1.14, 95% CI = 1.02 to 1.28) showed significantly higher clinical pregnancy rates with progestins. However, the quality of evidence is low. Studies comparing medroxyprogesterone acetate, dydrogesterone and micronized progesterone suggested similar ovarian response and pregnancy outcomes. The euploidy status of embryos from progestin primed cycles was similar to that of embryos from conventional stimulation cycles. Available information is reassuring regarding obstetric and neonatal outcomes with the use of progestins. Despite the lower cost of progestins than GnRH analogues, the mandatory cryopreservation of all embryos followed by a deferred transfer may increase cost per live birth with progestins as compared to an ART cycle culminating in a fresh ET.
WIDER IMPLICATIONS
Progestins can present an effective option for women who do not contemplate a fresh ET, e.g. fertility preservation, anticipated hyper responders, preimplantation genetic testing, oocyte donors, double stimulation cycles.
Topics: Female; Gonadotropin-Releasing Hormone; Humans; Ovulation Induction; Pregnancy; Pregnancy Rate; Progestins; Reproductive Techniques, Assisted
PubMed: 33016316
DOI: 10.1093/humupd/dmaa040 -
Breast Cancer Research and Treatment Sep 2020Approximately 70% of patients with metastatic breast cancer (MBC) are hormone receptor (HR)-positive. Recent studies have shown that CDK4/6 inhibitors (CDKI) improve... (Comparative Study)
Comparative Study Meta-Analysis
Venous thromboembolism risk in patients with hormone receptor-positive HER2-negative metastatic breast cancer treated with combined CDK 4/6 inhibitors plus endocrine therapy versus endocrine therapy alone: a systematic review and meta-analysis of randomized controlled trials.
PURPOSE
Approximately 70% of patients with metastatic breast cancer (MBC) are hormone receptor (HR)-positive. Recent studies have shown that CDK4/6 inhibitors (CDKI) improve survival in combination with ET in HR-positive, HER2-negative MBC. The risk of venous thromboembolism (VTE) is 3-4 times higher in patients with breast cancer (BC) than in patients without cancer. The risk is even higher in BC patients receiving ET and chemotherapy. The aim of the study was to determine the VTE risk of CDKIs plus ET versus ET alone in patients with HR-positive, HER2-negative MBC.
METHODS
We performed a systematic review and meta-analysis to demonstrate the risk of VTE in patients with HR-positive HER2-negative MBC treated with combined CDKIs and ET versus ET alone.
RESULTS
Eight randomized controlled trials (RCT) with a total of 4,557 patients were eligible. The study arms comprised of palbociclib or ribociclib or abemaciclib plus ET while the control arms utilized placebo plus ET. The VTE events were 56 (2%) in the CDKIs plus ET group compared to 10 (0.5%) in the control group. Pooled relative risk (RR) for VTE was 2.62 (95% CI 1.21-5.65; P = 0.01) and the risk difference (RD) was 0.01 (95% CI 0.00-0.03; P = 0.02). Over a median follow-up of up to 36 months, RR was 3.18 (95% CI 1.22-8.24; P = 0.02) and RD was 0.03 (95% CI 0.01-0.06, P = 0.008).
CONCLUSIONS
Our meta-analyses demonstrated that the addition of CDKIs to ET in patients with HR-positive HER 2-negative MBC contribute to a higher incidence of VTE. Further trials are required to define the actual relation and definitive incidence of VTE with different CDKIs.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Drug Therapy, Combination; Estrogen Receptor alpha; Female; Humans; Neoplasm Metastasis; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Receptors, Progesterone; Risk Factors; Venous Thromboembolism
PubMed: 32647939
DOI: 10.1007/s10549-020-05783-3 -
Current Problems in Cancer Dec 2020CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors are both emerging agents for hormonal receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy and safety of CDK4/6 and PI3K/AKT/mTOR inhibitors in women with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and network meta-analysis.
BACKGROUND
CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors are both emerging agents for hormonal receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer. Evidence for the comparisons from head-to-head comparative trials is currently insufficient. This meta-analysis assessed the comparative efficacy and safety of these two groups of agents for HR+/HER2- metastatic breast cancer.
METHODS
Systematic searches of PubMed, Embase, CENTRAL, SciSearch between January 2010 to December 2019 were conducted. Randomized controlled trials (RCTs) which evaluated clinical benefits and toxicities of CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors plus endocrine therapy were adopted. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoint was treatment-related adverse event (TRAE). Pooled hazard ratio (HR) and risk rate (RR) were used to assess the differences between CDK4/6 and PI3K/AKT/mTOR inhibitors.
RESULTS
A total of twenty RCTs including 9771 participants were identified in this study. Pooled results showed that PFS was considerably prolonged by targeted therapy plus endocrine therapy. PFS was relatively better in CDK4/6 inhibitors than that of PI3K inhibitor group (HR, 1.43; 95%CrI, 1.12-1.61). Similar results were demonstrated in results after balancing lines of therapy or metastatic sites, both in viscera and bone-only. Coalesced outcomes revealed that CDK4/6 inhibitors plus endocrine therapy could significantly improve OS (HR, 0.78; 95%CrI, 0.65-0.94) than PI3K/mTOR inhibitors. Safety profiles of diarrhea and rash were consistent between CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors with no difference of estimated RR. Several TRAEs signified specificity, for instance, myelosuppression in CDK4/6 inhibitors or hyperglycemia in PI3K/mTOR inhibitors.
CONCLUSIONS
Clinical efficacy is in favor of CDK4/6 inhibitors, and safety profiles are comparable between CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors plus endocrine therapy.
Topics: Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; TOR Serine-Threonine Kinases
PubMed: 32446638
DOI: 10.1016/j.currproblcancer.2020.100606 -
Clinical Breast Cancer Jun 2020PIK3CA mutations may have prognostic value for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer,...
PIK3CA mutations may have prognostic value for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer, representing an important potential target for systemic therapy. Prognostic and predictive values associated with PIK3CA mutations are not well understood. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and conference abstracts was performed for English-language articles published January 1993 through April 2019. Articles were categorized by treatment arms based on experimental and treatment drug classes. Information on progression-free survival (PFS), hazard ratios, overall survival, response rate, and clinical benefit rate was obtained. A total of 17 studies were included. Among those evaluating non-PI3Ki based therapies, 91% showed numerically shorter median PFS, ranging from 1.5 to 19.2 months and 1.8 to 29.6 months for the mutant versus non-mutant subgroups, respectively. Where reported (n = 13 studies), PFS was shorter between those arms offering endocrine monotherapy (range, 1.6-14.7 months) compared with a corresponding targeted therapy + endocrine monotherapy (range, 3.9-29.6 months). Of 5 PI3Ki-based arms comparing PFS, higher median PFS in PIK3CA mutant versus non-mutant cases was demonstrated. PFS was shorter for patients with PIK3CA mutant (range, 1.6-19.2 months) compared with PIK3CA wild-type (range, 1.8-29.6 months) in 10 (71%) of 14 treatment arms reporting PFS. Studies (n = 4) not reporting PFS reported response rate, but there were no clear directional trends. The presence of PIK3CA mutations may be associated with worse clinical outcomes in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Clinical outcomes such as PFS may be improved using a combination of PI3Ki-based therapies and endocrine therapies among this population. However, more research is warranted to fully elucidate this association.
Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast; Breast Neoplasms; Chemotherapy, Adjuvant; Class I Phosphatidylinositol 3-Kinases; Drug Resistance, Neoplasm; Female; Humans; Mastectomy; Mutation; Neoplasm Recurrence, Local; Predictive Value of Tests; Prognosis; Progression-Free Survival; Protein Kinase Inhibitors; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Risk Assessment
PubMed: 32234362
DOI: 10.1016/j.clbc.2019.08.011 -
Handbook of Experimental Pharmacology 2020Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone...
Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone acetate - DMPA), interfere with vitamin D levels (liver inducing anti-epileptic drugs), or directly by toxic effects on bone cells (chemotherapy, phenytoin, or thiazolidinedions, which diverts mesenchymal stem cells from forming osteoblasts to forming adipocytes). However, besides effects on the mineralized matrix, interactions with collagen and other parts of the unmineralized matrix may decrease bone biomechanical competence in a manner that may not correlate with bone mineral density (BMD) measured by dual energy absorptiometry (DXA).Some drugs and drug classes may decrease BMD like the thiazolidinediones and consequently increase fracture risk. Other drugs such as glucocorticoids may decrease BMD, and thus increase fracture risk. However, glucocorticoids may also interfere with the unmineralized matrix leading to an increase in fracture risk, not mirrored in BMD changes. Some drugs such as selective serotonin reuptake inhibitors (SSRI), paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs) may not per se be associated with bone loss, but fracture risk may be increased, possibly stemming from an increased risk of falls stemming from effects on postural balance mediated by effects on the central nervous system or cardiovascular system.This paper performs a systematic review of drugs inducing bone loss or associated with fracture risk. The chapter is organized by the Anatomical Therapeutic Chemical (ATC) classification.
Topics: Bone Density; Bone and Bones; Fractures, Bone; Humans; Medroxyprogesterone Acetate; Pharmaceutical Preparations
PubMed: 31889220
DOI: 10.1007/164_2019_340 -
Human Reproduction Update Jan 2020Freeze-all IVF cycles are becoming increasingly prevalent for a variety of clinical indications. However, the actual treatment objectives and preferred treatment...
BACKGROUND
Freeze-all IVF cycles are becoming increasingly prevalent for a variety of clinical indications. However, the actual treatment objectives and preferred treatment regimens for freeze-all cycles have not been clearly established.
OBJECTIVE AND RATIONALE
We aimed to conduct a systematic review of all aspects of ovarian stimulation for freeze-all cycles.
SEARCH METHODS
A comprehensive search in Medline, Embase and The Cochrane Library was performed. The search strategy included keywords related to freeze-all, cycle segmentation, cumulative live birth rate, preimplantation genetic diagnosis, preimplantation genetic testing for aneuploidy, fertility preservation, oocyte donation and frozen-thawed embryo transfer. We included relevant studies published in English from 2000 to 2018.
OUTCOMES
Our search generated 3292 records. Overall, 69 articles were included in the final review. Good-quality evidence indicates that in freeze-all cycles the cumulative live birth rate increases as the number of oocytes retrieved increases. Although the risk of severe ovarian hyperstimulation syndrome (OHSS) is virtually eliminated in freeze-all cycles, there are certain risks associated with retrieval of large oocyte cohorts. Therefore, ovarian stimulation should be planned to yield between 15 and 20 oocytes. The early follicular phase is currently the preferred starting point for ovarian stimulation, although luteal phase stimulation can be used if necessary. The improved safety associated with the GnRH antagonist regimen makes it the regimen of choice for ovarian stimulation in freeze-all cycles. Ovulation triggering with a GnRH agonist almost completely eliminates the risk of OHSS without affecting oocyte and embryo quality and is therefore the trigger of choice. The addition of low-dose hCG in a dual trigger has been suggested to improve oocyte and embryo quality, but further research in freeze-all cycles is required. Moderate-quality evidence indicates that in freeze-all cycles, a moderate delay of 2-3 days in ovulation triggering may result in the retrieval of an increased number of mature oocytes without impairing the pregnancy rate. There are no high-quality studies evaluating the effects of sustained supraphysiological estradiol (E2) levels on the safety and efficacy of freeze-all cycles. However, no significant adverse effects have been described. There is conflicting evidence regarding the effect of late follicular progesterone elevation in freeze-all cycles.
WIDER IMPLICATIONS
Ovarian stimulation for freeze-all cycles is different in many aspects from conventional stimulation for fresh IVF cycles. Optimisation of ovarian stimulation for freeze-all cycles should result in enhanced treatment safety along with improved cumulative live birth rates and should become the focus of future studies.
Topics: Birth Rate; Cryopreservation; Embryo Transfer; Embryo, Mammalian; Female; Fertilization in Vitro; Freezing; Genetic Testing; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Oocyte Donation; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Preimplantation Diagnosis
PubMed: 31867625
DOI: 10.1093/humupd/dmz037 -
Archives of Gynecology and Obstetrics Nov 2019Maintenance tocolysis, mostly defined as the continuation of tocolytic treatment beyond 48 h, remains a matter of debate. There is no sufficient evidence from...
INTRODUCTION
Maintenance tocolysis, mostly defined as the continuation of tocolytic treatment beyond 48 h, remains a matter of debate. There is no sufficient evidence from randomized controlled trials, that maintenance tocolysis is able to prolong pregnancy significantly and to reduce severe neonatal morbidity and mortality. Hence, it is not recommended in current guidelines. On the contrary, maintenance tocolysis is commonly used in clinical practice and subject of current clinical-scientific investigations.
TOCOLYTICS FOR MAINTENANCE TREATMENT
None of the conventional tocolytics (beta-sympathomimetics, calcium-channel blockers, magnesium, cyclooxygenase inhibitors, and oxytocin receptor antagonists) have proven to be appropriate for maintenance treatment. Progesterone and 17-α-hydroxyprogesterone caproate have shown promising results in low-quality randomized trials, but not in high-quality studies.
DISCUSSION
Basically, the value of studies regarding maintenance tocolysis is limited by a considerable heterogeneity, its mostly low quality, significant differences in methodology as well as the inadequate statistical power due to the small number of women studied. So far, maintenance tocolysis is a case-by-case decision outweighing the benefits and harms of tocolytic treatment.
Topics: Female; Humans; Obstetric Labor, Premature; Pregnancy; Progesterone; Randomized Controlled Trials as Topic; Tocolysis; Tocolytic Agents
PubMed: 31576452
DOI: 10.1007/s00404-019-05313-7