Harms of third- and fourth-generation combined oral contraceptives in premenopausal women: A systematic review and meta-analysis.

We assessed the available evidence regarding adverse effects on surrogate and patient-important health outcomes of third- and fourth-generation combined oral contraceptives among premenopausal women. We performed a systematic review and meta-analysis including randomized controlled trials and observational studies comparing third- and fourth-generation combined oral contraceptives with other generation contraceptives or placebo. Studies that enrolled women aged 15 to 50 years, with at least three cycles of intervention and 6 months of follow-up were included. A total of 33 studies comprising 629,783 women were included. Low-density lipoprotein cholesterol levels were significantly lower in fourth-generation oral contraceptives (mean differences (MD): -0.24 mmol/L; [95% CI -0.39 to -0.08]), while total cholesterol was significantly increased in levonorgestrel users when compared to third-generation oral contraceptives (MD: 0.27 mmol/L; [95% CI 0.04 to 0.50]). A decreased arterial thrombosis incidence was shown in fourth-generation oral contraceptive users, as compared to levonorgestrel (incidence rate ratio (IRR): 0.41; [95% CI 0.19 to 0.86]). No difference was found in the occurrence of deep venous thrombosis between fourth-generation oral contraceptives and levonorgestrel users (IRR: 0.91; [95% CI 0.66 to 1.27]; p = 0.60; I2 = 0%). Regarding the remaining outcomes, data were heterogeneous and showed no clear difference. In premenopausal women, the use of third- and fourth-generation oral contraceptives is associated with an improved lipid profile and lower risk of arterial thrombosis. Data were inconclusive regarding the rest of outcomes assessed. This review was registered in PROSPERO with CRD42020211133.

The Effects of Preimplantation Genetic Testing for Aneuploidy (PGT-A) on Patient-Important Outcomes in Embryo Transfer Cases: A Meta-Analysis.

Background: The aim of this study was to evaluate the effect of preimplantation genetic testing for aneuploidy (PGT-A) on patient-important reproductive outcomes after in vitro fertilization (IVF). Methods: Randomized and non-randomized studies have been sought in Ovid, MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials since each database's inception through May 2021. Main keywords used for the search strategy included "Embryo transfer", "In vitro fertilization", "DNA sequencing", and "Comparative genome hybridization". Studies were screened independently and in duplicate. Results: Ten studies were finally analyzed, representing a total of 2630 embryo transfers. The pooled OR for live birth rates were 1.45 (95%CI 0.24-8.78, I2 96%) and 1.66 (95%PI 0.15-18.01, 95%CI 0.98-2.83, I2 81%) derived from the NRSIs and the RCTs, respectively, in which the miscarriage rate were 1.25 (95%CI 0.19-8.33, I2 70%) and 0.57 (95%PI 0.06-5.34, 95%CI 0.27-1.21, I2 53%), and clinical pregnancy rates were 3.08 (95%CI 2.22-4.29, I2 0%) and 1.43 (95%PI 0.38-5.42, 95%CI 0.96-2.13, I2 68%). Influence analyses showed a greater treatment effect when excluding studies without patients at advanced maternal age. Conclusion: There seems to be no significant difference in reproductive outcomes when using PGT-A in the general population; however, the procedure seems advantageous for patients at advanced maternal age. Nevertheless, this warrants caution when recommending the procedure to all couples seeking ART, as the current possible benefits may not justify the additional costs for all groups of patients.

The Effect of Post warming Culture Period Between Thawing and Transfer of Cryopreserved Embryos on Reproductive Outcomes After In Vitro Fertilization (IVF): A Systematic Review and Meta-analysis.

BACKGROUND: The purpose of this study was to evaluate the effect of post warming culture period between thawing and transfer of cryopreserved embryos on reproductive outcomes after in vitro fertilization (IVF). METHODS: An extensive literature search was performed using PubMed, EmBase, and the Cochrane library from January 2000 to August 2019. A systematic review and meta-analysis of clinical trials was performed in this manuscript. The trials represented patients with embryo transfers of at least one previously cryopreserved good quality embryo. Main outcome measures of the study included clinical pregnancy rate, live birth rate, miscarriage rate, and ectopic pregnancy rate. RESULTS: A total of 5338 trial/abstracts were identified through a literature search. Totally, five studies were included in the systematic review, and three in the final meta-analysis. The studies included 1717 embryo transfers, 605 after short culture, and 1112 after long culture. The clinical pregnancy rate (CPR) was the most consistent outcome reported. The CPR was slightly better after short time culture with a RR of 1.09 (0.95-1.26, 95%CI) but this difference was not statistically significant. The great heterogenicity in the results reported in the included studies made it impossible to compare all planned outcomes. CONCLUSION: There are no differences in reproductive outcomes if cryopreserved embryos are transferred after overnight culture or after two hours of culture following thawing. Due to small number and the poor quality of trials reported on this topic, the results of this review should be treated with caution.

Association between thyroid autoimmunity and ovarian reserve in women with hypothyroidism.

BACKGROUND: The ovarian function and therefore the ovarian reserve may be compromised by the pathogenesis of autoimmune diseases of which, Hashimoto's thyroiditis (HT) is the most common in women of reproductive age. Furthermore, a prolonged reduction in thyroid hormone concentration results in a broad spectrum of reproductive alteration. Previous reports in the literature have been controversial regarding the impact of hypothyroidism and alterations in the ovarian reserve. Thus, this prospective and comparative study aimed to evaluate the association of hypothyroidism with low ovarian reserve. MATERIALS AND METHODS: A subset of 27 patients with primary autoimmune hypothyroidism were compared to healthy women. The ovarian reserve was assessed through the anti-Mullerian hormone (AMH) and the antral follicle count (AFC). RESULTS: Overall, the two groups did not display significant differences in length of their menstrual cycles neither in the AMH serum levels nor the AFC. CONCLUSIONS: No significant alteration was found in the ovarian reserve of women with HT.

Clinical Pregnancy After Elimination of Embryo Fragments Before Fresh Cleavage-stage Embryo Transfer.

Objective: To determine if the elimination of fragments in cleavage-stage embryos, before fresh transfer, improves pregnancy rates in in vitro fertilization cycles. Materials and methods: This is a Prospective observational case-control study carried out at a University Reproductive Center. We included Twenty-six infertile patients divided into two groups. Group one: 13 patients with embryos classified as grade B and C (embryos with fragments) according to the Hill classification, and Group two: 13 patients with grade A embryos (embryos with no fragments). Embryo Defragmentation was performed in embryos of group one 65 to 68 hours after conventional fertilization. Fresh embryo transfer was made after two hours post fragments removal. Reproductive results were evaluated and compared between both groups. Results: The total number of clinical pregnancies was nine. In group one there were 5 (38.5 %); in group two, there were 4 (30.8%). The difference was not statistically significant (p = 0.68). Two abortions were reported in the study, both in group one; were fragment elimination was performed. This represents an abortion rate of 40% in patients who got pregnant in this group. These patients had twice the probability of suffering an abortion (OR 2.1; 95% CI 1.4-3.37). Ongoing pregnancies were similar in both groups. Conclusion: Removal of fragments in freshly transferred day three embryos could be an alternative to increase clinical pregnancy and ongoing pregnancy rates in patients who have only poor-quality embryos. Despite the relationship with a higher abortion rate, this strategy could represent a real alternative for this type of patient.