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.

Evaluation of the Ovarian Reserve in Women With Systemic Lupus Erythematosus.

Objective: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder where the disease activity itself and the medications used for its treatment, may have adverse effects on ovarian function. This study aimed to assess the ovarian reserve (OR) in SLE patients. Materials and methods: The anti-müllerian hormone (AMH) and the antral follicle count (AFC), two markers to evaluate the OR was assessed in 64 SLE patients and compared to normal individuals. Additionally, we assessed whether the disease per se or the pharmacological treatments affect the OR. Results: Patients with SLE displayed alterations in the OR regardless of the presence of alterations of the menstrual cycle. The AFC and AMH were significantly lower in SLE patients with and without menstrual alterations when compared to control individuals (p<0.0001). However, the AFC and AMH levels were significantly correlated (p=0.006) in the SLE patients with menstrual alterations. Except for hydroxychloroquine that was statistically higher in SLE patients with menstrual alterations (p=0.04), the cumulative dose for cyclophosphamide, corticosteroid, and methotrexate was similar in SLE patients regardless of the occurrence of menstrual alterations. Conclusion: The monitoring of AMH and AFC in SLE patients should be used to detect the rapid and irreversible decline of the OR to provide a possibility of pregnancy to the SLE 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.

Evaluation of Ovarian Reserve in Women With Rheumatoid Arthritis.

Objective: Subfertility is commonly observed in patients with rheumatoid arthritis (RA). Although the causes are not well established, the alteration of the ovarian reserve is thought to contribute to the lower chances of pregnancy. This cross-sectional study aimed to evaluate the ovarian reserve in patients with RA. Materials and methods: Two parameters associated with ovarian reserves such as the antral follicle count (AFC) and the anti-müllerian hormone (AMH) were assessed in 38 patients with RA. We also analyzed the correlation of these parameters with the medication used to treat this pathology and with the illness severity. Results: The AMH levels in women with RA were comparable to those found on healthy individuals although the RA patients were more likely to have a low AFC. Ovarian reserve and RA were neither influenced by parameters of disease activity nor by the use of medication. Conclusion: The ovarian reserve in women with RA was similar to that found in healthy individuals.

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.

The elimination of apoptotic sperm in IVF procedures and its effect on pregnancy rate.

OBJECTIVE: To identify the effect of apoptotic sperm elimination with MACS in patients that require IVF. METHODS: An experimental, cross-sectional, descriptive, prospective and non-blinded study of diagnostic tests performed in patients who required IVF and ICSI from July 2011 to July 2012. Ninety-two couples participated according to the treatment administered to the semen sample; in the control group: the samples were subjected only to density gradients before ICSI, in the study group: the same procedure was performed plus the addition of the MACS technique. Comparing the groups, we assessed the fertilization, division, viable embryos and clinical pregnancy rates in all cases. RESULTS: We found significant differences when using MACS technique in sperm parameters. We found no differences between the total samples of the control and study groups. When separating the own and donated eggs in each group, we found an improvement in the fertilization rates (p<0.001) of the own eggs. In both groups, the handling of donated eggs lead to a significant improvement in the immunological pregnancy test (IPT) and fetal heart rate (FHR) results. Only in the donated eggs group, where MACS was applied, could we see that all cases with positive IPT had a fetal heart rate, which shows a significant difference (p<0.002) when compared with the control group, where the percentage decreased abruptly. CONCLUSIONS: This study demonstrates the effectiveness of the use of annexins (MACS) in eliminating apoptotic sperm, and when the obtained sperm is applied to good-quality eggs.

Ovarian and adrenal androgens and their link to high human chorionic gonadotropin levels: a prospective controlled study.

Background. Although the association between human chorionic gonadotropin (hCG) and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM). Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (P ≤ 0.001). Free testosterone (T) and dehydroepiandrosterone sulfate (DHEA-S) were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 µ/dL) when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 µ/dL) (P = 0.0001 and 0.001), respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (r = 0.78; P ≤ 0.001, r = 0.74; P ≤ 0.001, and r = 0.71; P ≤ 0.001), respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels (P = 0.001) and free T and DHEA-S declined significantly (P = 0.0002 and 0.009). Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction.

Embarazo ectópico molar cornual: caso clínico / Molar cornual ectopic pregnancy: clinical case

Antecedentes: La incidencia de embarazo ectópico es 20/1000 embarazos y en la región cornual se presentan en el 2-4 por ciento. La mola hidatiforme ocurre en 1/1000 embarazos en EEUU y 1/500 en México. La presentación simultánea es muy rara. Se han descrito solamente 40 casos en la literatura médica, con una incidencia estimada de 0,04 por ciento de localización cornual. Caso clínico: Primigesta de 30 años, que cursando un embarazo de 8 semanas, acude de urgencia por presentar náuseas y vómitos de 1 día de evolución, con dolor abdominal y sangrado vaginal. Prueba de embarazo positiva. A la exploración física presenta dolor abdominal difuso y signos de irritación peritoneal. El ultrasonido transvaginal mostró imagen ecogénica multiquística intrauterina cercana a la región cornual, por lo que se sospecha embarazo molar. En la laparotomía exploradora se realizó resección cornual y posteriormente dilatación y curetaje de la cavidad uterina. La anatomía patológica confrmó el diagnóstico. Negativizó beta-hGC a las 7 semanas después de la cirugía.

Background: The incidence of ectopic pregnancy is 20 per 1,000 pregnancies. The cornual ectopic pregnancy is found in 2-4 percent. Hydatidiform moles occur in 1 per 1000 pregnancies in USA and 1 per 500 in Mexico. Thus, the incidence of the two occurring together is very rare. Only 40 cases have been reported in the medical literature, the incidence estimate is 0.04 percent. Clinic case: We analyzed a 30 year old woman patient case, gravida 1, with 8 weeks' gestation by last menstrual period, came at the Hospital Universitario Dr. José Eleuterio González, Monterrey, Nuevo León, with complaints of nausea and vomiting for 1 day and abdominal pain, and transvaginal bleeding. A cualitative pregnancy test was positive. Physical examination revealed diffuse abdominal tenderness and peritoneal signs. The transvaginal ultrasonography showed a multicystic echogenic mass within the uterus near cornual region consistent with a molar pregnancy. A cornual resection was performed followed by dilation and curettage. Pathologic diagnosis was confrmed. The monitoring of beta-hGC titers was negative 7 weeks after surgery.

[In vivo effect of endometria's and human cervix's secretions on the spermatozoid]. / Efecto in vivo de las secreciones del endometrio y del cuello uterino humano en el espermatozoide.

OBJECTIVE: To demonstrate the capacitance stages acquired by the spermatozoa after the in vivo contact with the endometrium and the human cervical canal. STUDY TYPE: Experimental, prospective, and longitudinal. MATERIALS AND METHODS: Spermatozoa obtained from the cervix and endometrium, plus post-capacitated semen in a 1 and 4 hours process, from couples that have proved fertility, were processed to evaluate motility, morphology, vitality and identification of morphological patterns with chlortetracycline and then inducted to acrosomal reaction with ionophore A23187. RESULTS: A safe, fast and harmless technique to obtain endometrial secretions is described. The spermatozoa capacitated in vitro and in vivo developed specific capacitance stages, applying Perry's patterns with the CTC test. Spermatozoa capacitated in vitro and then recovered in the cervix responded favorably to the induction of the acrosomal reaction with calcium ionophore A23187, differing from the obtained with endometrium wash. CONCLUSIONS: The spermatozoa recovered from the endometrium presented a more advanced capacitance stage than that obtained from the cervix, this is demonstrated with the induction of the acrosomal reaction and the CTC test. These findings suggest that endometrial and cervical tissues promote capacitance, different in each one of them and progressive in their biological route.