Impact of chronic endometritis in infertility: a SWOT analysis.

Chronic endometritis is a pathology often associated with reproductive failure, but there are still no clear recommendations on whether its inclusion in the initial study of infertile couples is necessary. In this discussion paper, based on a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis, the different aspects of the repercussions of chronic endometritis in fertility are evaluated. To avoid possible subjectivity in the analysis and results of this study, the researchers followed the Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed literature seem to indicate that, pending new evidence, it would be advisable not to include chronic endometritis in the initial baseline study before assisted reproduction in order not to delay other assisted reproduction treatments. However, it would be advisable in cases of repetitive implantation failure and pregnancy loss after having undergone IVF with viable embryos and before continuing with costly reproductive processes, since results could be improved. The development of randomized studies assessing the impact of antibiotic treatment as a possible therapeutic option in infertile women with chronic endometritis, as well as the possible impact on endometrial microbiota and receptivity/implantation, would allow for the establishment of more precise clinical guidelines in this regard.

Correction to: Risk of adverse perinatal outcomes after oocyte donation: a systematic review and meta-analysis.

The original article unfortunately contained a mistake. the authors have written the wrong volume/issue/pages.

Risk of adverse perinatal outcomes after oocyte donation: a systematic review and meta-analysis.

RESEARCH QUESTION: In women with singleton pregnancies conceived after assisted reproductive technologies, does the in vitro fertilization with oocyte donation (IVF-OD) affect the perinatal and maternal outcomes compared to autologous in vitro fertilization (IVF-AO)? DESIGN: Systematic review and meta-analysis of studies comparing perinatal and maternal outcomes in singleton pregnancies resulting from IVF-OD versus IVF-AO. An electronic literature search in Pubmed, MEDLINE, and Cochrane database was performed. The main outcome measures were hypertensive disorders in pregnancy, preeclampsia, severe preeclampsia, pregnancy-induced hypertension, preterm birth, early preterm birth, low birth weight, and very low birth weight. RESULTS: Twenty-three studies were included. IVF-OD is associated with a higher risk of hypertensive disorders in pregnancy (OR 2.63, 2.17-3.18), preeclampsia (OR 2.64; 2.29-3.04), severe preeclampsia (OR 3.22; 2.30-4.49), pregnancy-induced hypertension (OR 2.16; 1.79-2.62), preterm birth (OR 1.57; 1.33-1.86), early preterm birth (OR 1.80; 1.51-2.15), low birth weight (OR 1.25, 1.20-1.30), very low birth weight (OR 1.37, 1.22-1.54), gestational diabetes (OR 1.27; 1.03-1.56), and cesarean section (OR 2.28; 2.14-2.42). There was no significant difference in the risk of preterm birth or low birth weight when adjusted for preeclampsia. CONCLUSIONS: IVF-OD patients should be considered an independent risk factor for some adverse perinatal outcomes, mainly hypertensive disorders in pregnancy, preeclampsia, and severe preeclampsia. Immunological and hormonal aspects may be involved in these results, and further research focusing in the etiopathogenesis of these pathologies are needed.

Laparoscopic Roux-en-Y gastric bypass vs. laparoscopic sleeve gastrectomy for morbid obesity: a systematic review and meta-analysis of lipid effects at one year postsurgery.

INTRODUCTION: Results of the effects of Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG) on triglyceride and high-density lipoprotein (HDL) cholesterol levels are controversial. Moreover, previous meta-analyses focused on global dyslipidemia remission, but did not include the separate remission rates of the different lipid fractions. Hence, the aim of the present meta-analysis was to compare the outcomes (concentration change and remission rates) of GB and SG on diverse lipid disorders one year postbariatric surgery (BS). EVIDENCE ACQUISITION: An exhaustive electronic search carried out on MedLine, Embase and The Cochrane Central Register of Controlled Trials (Central) until July 2016 yielded 2621 records, of which 17, totaling 4699 obese patients with one-year follow-up after BS were included in the meta-analysis. EVIDENCE SYNTHESIS: GB was superior to SG in terms of total cholesterol (mean difference= 19.77 mg/dL, 95% CI: 11.84-27.69) and low-density lipoprotein (LDL) cholesterol (mean difference: 19.29 mg/dL, 95% CI: 11.93-26.64) decreases as well as in hypercholesterolemia remission (RR: 1.43, 95% CI: 1.27-1.61). No differences were found between GB and SG in terms of HDL cholesterol increase or triglyceride concentration change after surgery, as well as in hypertriglyceridemia and low HDL remission rates. CONCLUSIONS: The effect of GB on total and LDL cholesterol concentration decreases and remission was greater than that of SG, whereas no differences were observed with respect to HDL cholesterol and triglyceride concentration evolution. Conclusions cannot be drawn from hypertriglyceridemia and low HDL remission rates based on this meta-analysis.

Perinatal outcomes in children born after fresh or frozen embryo transfer: a Catalan cohort study based on 14,262 newborns.

OBJECTIVE: To ascertain whether perinatal outcomes are affected by vitrification and/or controlled ovarian hyperstimulation (COH). DESIGN: Register-based cohort study. SETTING: Not applicable. PATIENT(S): Women undergoing in vitro fertilization (IVF) between 2008 and 2012 using autologous or donated eggs who had a singleton pregnancy delivered from the 24th week onward. INTERVENTION(S): Fresh embryo transfer (ET) or frozen-thawed ET in women undergoing IVF. MAIN OUTCOME MEASURE(S): Primary outcome birthweight, and secondary outcomes gestational age at delivery, small for gestational age, mode of delivery, and perinatal mortality. RESULT(S): In the autologous egg population, newborns from the fresh ET group had lower birthweight than the frozen-thawed ET group (3,152.9 ± 545.5g and 3,343.2 ± 532.3g, respectively), and this difference persisted even after adjusting for confounding factors, and the newborns had a higher risk of being small for gestational age (SGA). In contrast, among egg-donor recipients undergoing ET, the mean birthweight did not differ between the groups (3,165 ± 604.15 g and 3,143.60 ± 604.21g in the fresh and frozen-thawed ET groups, respectively); however, in the adjusted regression model birthweight was statistically significantly higher in the fresh ET group than the frozen-thawed ET group. The risk of SGA remained comparable between the fresh versus frozen-thawed ET groups. We observed no statistically significant differences in perinatal mortality between groups either in the autologous egg population or in the donor recipient group. CONCLUSION(S): Perinatal outcomes are negatively affected by COH and not affected by the vitrification process.

Low-dose growth hormone supplementation increases clinical pregnancy rate in poor responders undergoing in vitro fertilisation.

Poor ovarian response (POR) often means low success rates after in vitro fertilisation (IVF). We aim to study the impact of a low-dose growth hormone (GH) supplementation in pregnancy rates in poor responders in a prospective, self-controlled study of 64 poor responders to previous IVF cycles, who failed to achieve pregnancy and were supplemented with low-doses of GH in a subsequent cycle using the same gonadotropin dose and protocol. Our primary endpoint was the clinical pregnancy rate (CPR), considering secondary endpoints, the number of retrieved oocytes, embryos, embryo quality and the proportion of cycles with embryo transfer. CPR in the GH group was 34.4%. Significant differences were observed for the GH group both in the number of top quality embryos (0.64 ± 0.88 versus 1.03 ± 1.17, p < 0.05) and cryopreserved embryos (0.3 ± 0.81 versus 0.85 ± 1.49, p < 0.05). This is, to our knowledge, the first clinical trial to use a low dose of GH as a supplement for IVF in POR patients. Despite this low dose, we achieved excellent success rates in patients with a very poor prognosis, at a reasonable cost and without side effects, which makes this a safe and cost-effective alternative.

Oral antioxidant treatment partly improves integrity of human sperm DNA in infertile grade I varicocele patients.

Infertile males with varicocele have the highest percentage of sperm cells with damaged DNA, compared to other infertile groups. Antioxidant treatment is known to enhance the integrity of sperm DNA; however, there are no data on the effects in varicocele patients. We thus investigated the potential benefits of antioxidant treatment specifically in grade I varicocele males. Twenty infertile patients with grade I varicocele were given multivitamins (1500 mg L-Carnitine, 60 mg vitamin C, 20 mg coenzyme Q10, 10 mg vitamin E, 200 µg vitamin B9, 1 µg vitamin B12, 10 mg zinc, 50 µg selenium) daily for three months. Semen parameters including total sperm count, concentration, progressive motility, vitality, and morphology were determined before and after treatment. In addition, sperm DNA fragmentation and the amount of highly degraded sperm cells were analyzed by Sperm Chromatin Dispersion. After treatment, patients showed an average relative reduction of 22.1% in sperm DNA fragmentation (p = 0.02) and had 31.3% fewer highly degraded sperm cells (p = 0.07). Total numbers of sperm cells were increased (p = 0.04), but other semen parameters were unaffected. These data suggest that sperm DNA integrity in grade I varicocele patients may be improved by oral antioxidant treatment.

Random-start GnRH antagonist for emergency fertility preservation: a self-controlled trial.

The aim of this study is to evaluate the feasibility and safety of random-start controlled ovarian hyperstimulation (COH) for emergency fertility preservation, regardless of the phase of the menstrual cycle. A self-controlled pilot clinical trial (NCT01385332) was performed in an acute-care teaching hospital and in two private reproductive centers in Barcelona, Spain. Eleven egg donors participated in the study. Two random-start gonadotropin-releasing hormone (GnRH) antagonist protocols were assessed in which ganirelix was initiated on either day 10 (protocol B) or on day 20 (protocol C) of the menstrual cycle and was continued until estradiol levels were below 60 pg/dL. These protocols were compared with a standard protocol (protocol A). The main outcome of interest was the number of metaphase 2 oocytes retrieved. Results from this study show that the number of mature oocytes retrieved was comparable across the different protocols (14.3±4.6 in the standard protocol versus 13.0±9.1 and 13.2±5.2 in protocols B and C, respectively; values expressed as mean ± standard deviation). The mean number of days needed for a GnRH antagonist to lower estradiol levels, as well as the ongoing pregnancy rates, were also similar when protocols B (stimulation in follicular phase) and C (stimulation on luteal phase) were compared with protocol A (standard stimulation). GnRH antagonists can be effectively used for random-start controlled ovarian hyperstimulation with an ovarian response similar to that of standard protocols, and the antagonists appear suitable for emergency fertility preservation in cancer patients.

"20209C-T" a variant mutation of prothrombin gene mutation in a patient with recurrent pregnancy loss.

Recurrent pregnancy loss is considered when a female undergoes at least two consecutive, spontaneous abortions or more than two alternatively. This condition affects approximately 5% of women in reproductive age. Several causes of recurrent abortion have been established, but nevertheless, approximately half of all cases remain unexplained. Thrombophilic disorders have been suggested as a possible cause of recurrent miscarriage. A single 20210 G-A mutation of the 3'-untranslated region of (F2) has been reported as a cause of inherited thrombophilia. The F2 G-A mutation affects 1% to 4% of the US population, and its prevalence is higher among Caucasian women of Southern European descendants. Studies of G20210A polymorphism have also shown conflicting associations with recurrent abortions. In addition to G20210A polymorphism, other mutations affecting the F2 gene have been associated with thrombosis and/or pregnancy complications.

Multiple determinations of sperm DNA fragmentation show that varicocelectomy is not indicated for infertile patients with subclinical varicocele.

Varicocele is one of the most common causes of low semen quality, which is reflected in high percentages of sperm cells with fragmented DNA. While varicocelectomy is usually performed to ameliorate a patient's fertility, its impact on sperm DNA integrity in the case of subclinical varicocele is poorly documented. In this study, multiple DNA fragmentation analyses (TUNEL, SCD, and SCSA) were performed on semen samples from sixty infertile patients with varicocele (15 clinical varicoceles, 19 clinical varicoceles after surgical treatment, 16 subclinical varicoceles, and 10 subclinical varicoceles after surgical treatment). TUNEL, SCD, and SCSA assays all showed substantial sperm DNA fragmentation levels that were comparable between subclinical and clinical varicocele patients. Importantly, varicocelectomy did improve sperm quality in patients with clinical varicocele; however, this was not the case in patients with subclinical varicocele. In summary, although infertile patients with clinical and subclinical varicocele have similar sperm DNA quality, varicocelectomy should only be advised for patients with clinical varicocele.

Efficacy of luteal phase support with vaginal progesterone in intrauterine insemination: a systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of luteal phase support with vaginal progesterone in women undergoing intrauterine insemination (IUI). METHODS: Systematic review and meta-analysis. Randomized controlled trials (RCT) comparing supplementation of luteal phase with vaginal progesterone among women undergoing IUI versus a control group were included. The main outcome assessed was live birth rate. RESULTS: Five RCT met the inclusion criteria. In all 1,271 patients were included (951 IUI cycles in the progesterone group, 935 in the control group). Women treated with vaginal progesterone achieved significantly higher live birth rate (risk ratio [RR] 1.94, 95 % confidence interval [CI] 1.36 to 2.77,), and clinical pregnancy rate (RR 1.41, 95 % CI 1.14 to 1.76) as compared with controls. In the subgroup analysis per stimulation protocol, this beneficial effect of receiving progesterone was only observed in the group stimulated with gonadotropins (RR 2.28, 95 % CI 1.49 to 3.51), compared to the group stimulated with clomiphene citrate (CC) (RR 1.30, 95 % CI 0.68 to 2.50). No differences were observed in the miscarriage and multiple pregnancy rates. CONCLUSIONS: The supplementation of luteal phase with vaginal progesterone significantly increases live birth among women undergoing IUI when receiving gonadotropins for ovulation induction. Women receiving CC to induce ovulation do not seem to benefit from this treatment.

Diagnostic value of sperm DNA fragmentation and sperm high-magnification for predicting outcome of assisted reproduction treatment.

Over the last years, major improvements in the field of male infertility diagnosis have been achieved. The aim of this study was to determine the diagnostic usefulness of sperm DNA integrity and sperm vacuolisation for predicting outcome in infertile couples undergoing in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) treatments. A cohort study from 152 infertile couples undergoing sperm DNA fragmentation and high-magnification tests prior to an assisted reproduction treatment was designed. We found that the most predictive cutoff for pregnancy was 25.5% of DNA fragmentation with a negative predictive value of 72.7% (P=0.02). For the degree of vacuolisation, the best predictor of pregnancy was 73.5% of vacuolated sperm grades III+IV with a negative predictive value of 39.4% (P=0.09), which was not statistically significant. In conclusion, sperm DNA fragmentation greater than 25.5% could be associated with higher probability of failure IVF treatment. Regarding the results of the sperm analysis at high magnification, they do not allow us to predict whether or not patients will become pregnant.

Coenzyme Q10 and male infertility: a meta-analysis.

OBJECTIVE: To evaluate the effect of coenzyme Q10 treatments in male infertility, specifically in these parameters: live birth and pregnancy rates, CoQ10 seminal concentration, sperm concentration, and sperm motility. MATERIALS AND METHODS: Systematic review and meta-analysis in male infertility patients with CoQ10 oral treatments. Three trials were included: 149 males in CoQ10 group and 147 males in placebo group. RESULTS: None of the included trials provided any data regarding live births. The results of this meta-analysis show that supplementing infertile men with CoQ10 does not increase pregnancy rates. The analysis showed, among patients receiving CoQ10 treatment, a statistically significant increase in: CoQ10 seminal concentration (RR 49.55, 95 % CI 46.44 to 52.66, I(2) = 17 %), sperm concentration (RR 5.33, 95 % CI 4.18 to 6.47, I(2) = 58 %), and sperm motility (RR 4.50, 95 % CI 3.92 to 5.08, I(2) = 0 %) CONCLUSION: There is no evidence in the literature that CoQ10 increases either live birth or pregnancy rates, but there is a global improvement in sperm parameters. Adequately powered, robust trials of individual and combination antioxidant therapies are required to guide clinical practice.

Medical alternatives to oocyte donation in women with premature ovarian failure: a systematic review.

Oocyte donation can satisfy the desire to have children in women with premature ovarian failure (POF) but little progress has been made to improve reproduction using the patients' own gametes. The aim of this study was to assess the effectiveness of alternative treatments to oocyte donation in patients with POF. A systematic search of MEDLINE, EMBASE and Cochrane databases from January 1988 to January 2012 using descriptors related to POF, ovulation induction, and pregnancy was made. Randomized clinical trials of women with POF undergoing various treatments to achieve ovulation induction, often compared with alternative treatment and placebo groups, were only selected. Outcomes of interest were those related to pregnancy (biochemical and live birth). Twelve trials were included and analysed for methodology, inclusion and exclusion criteria, number of patients included, characteristics and type of intervention, and results in terms of ovulation rate, pregnancy rate and ongoing pregnancy rate. The large methodological variability among studies prevented to combined data for a meta-analysis. None of the studies showed statistically significant differences between the study groups. The lack of case-control studies with a placebo group makes it impossible to establish differences between a treatment and no treatment.

Effects of transdermal testosterone in poor responders undergoing IVF: systematic review and meta-analysis.

A systematic review and meta-analysis was performed to evaluate the effect of transdermal testosterone preceding ovarian stimulation in women with poor ovarian response undergoing IVF. Studies comparing pretreatment with transdermal testosterone versus standard ovarian stimulation among poor responders were included. The main outcome assessed was live birth. Three trials were included (113 women in the testosterone group, 112 in the control group). Testosterone-treated women achieved significantly higher live birth rate (risk ratio, RR, 1.91, 95% CI 1.01 to 3.63), clinical pregnancy rate (RR 2.07, 95% CI 1.13 to 3.78) and required significantly lower doses of FSH (RR -461.96, 95% CI -611.82 to -312.09). However, differences observed in clinical pregnancy per embryo transferred were not statistically significant (RR 1.72, 95% CI 0.91 to 3.26). No differences were observed regarding number and quality of the oocytes retrieved. In conclusion, transdermal testosterone significantly increases live birth and reduces the doses of FSH required. These findings support the theoretical synergistic role of androgens and FSH on folliculogenesis. The present data should be interpreted with caution because of the small number of trials and clinical heterogeneity. The identification of poor responders that could especially benefit from testosterone treatment should be addressed in further studies. The poor response to ovarian stimulation among women undergoing IVF is of great concern in reproductive medicine. Certain modalities have been tested to improve this response to gonadotrophin stimulation, although results from some studies have shown conflicting results. Hence, a systematic review and meta-analysis was performed in order to evaluate the effect of transdermal testosterone prior to ovarian stimulation among these women with poor ovarian response. The main outcome assessed was live birth rate. In all, three trials were included, which comprehended 113 women in the testosterone group and 112 in the control group. Women that were pretreated with transdermal testosterone achieved significantly higher live birth rate and clinical pregnancy rate and required significantly lower doses of exogenous FSH as compared with controls. However, when clinical pregnancy rate was adjusted per embryo transferred differences observed were not statistically significant. No differences were observed in the number and quality of the oocytes retrieved. In conclusion, transdermal testosterone prior to ovarian stimulation significantly increases live birth and reduces the doses of FSH required among poor responders. In addition, the identification of poor responders that could especially benefit from testosterone treatment should be addressed in further studies.

Efficacy and safety of human chorionic gonadotropin for follicular phase stimulation in assisted reproduction: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of hCG to induce follicular stimulation. DESIGN: Systematic literature searches of PubMed, EMBASE, CENTRAL, and SciSearch databases. Randomized controlled trials (RCTs) using hCG in early or late follicular phases were included. SETTING: Three reproductive medicine services of gynecology in Spain and two universities. PATIENT(S): A total of 1,068 women treated in 11 RCTs were included. INTERVENTION(S): Use of hCG versus other hormone treatments, no administration, or placebo during the period of follicular stimulation. MAIN OUTCOME MEASURE(S): Live birth, clinical pregnancy, mature oocytes, miscarriage, ovarian hyperstimulation syndrome (OHSS), and FSH doses. RESULT(S): No differences in live birth, miscarriage, and OHSS rates between hCG (given at either the early or late follicular phases) and different control regimens were found. Pooled analysis for clinical pregnancy showed significant differences in favor of hCG at the late follicular phase. The doses of FSH were lower in women treated with hCG at either the early or late follicular phase than in those treated with FSH alone. CONCLUSION(S): The use of hCG in the early and late follicular phase in controlled ovarian stimulation has the advantage of decreasing the doses of FSH.

Hirsutism scoring in polycystic ovary syndrome: concordance between clinicians' and patients' self-scoring.

In a clinical series of 68 women with polycystic ovary syndrome in which the reason for consultation was hirsutism, the mean (standard error of the mean) hirsutism score of the modified Ferriman-Gallwey method was 15.1 (6.8), compared with 12.0 (4.4) for clinicians' scoring. In the multivariable analysis, clinicians' scoring of hirsutism was the only independent variable significantly associated with increased testosterone free index levels.

Antral follicle count as a predictor of hyperresponse in controlled ovarian hyperstimulation/intrauterine insemination in unexplained sterility.

In this prospective study of women with unexplained infertility undergoing the first cycle of controlled ovarian hyperstimulation/intrauterine insemination, the presence of 16 or more antral follicles on day 3 of the cycle was a good predictor of cancellation due to hyperresponse.

IVF/ICSI with or without preimplantation genetic screening for aneuploidy in couples without genetic disorders: a systematic review and meta-analysis.

PURPOSE: To assess the efficacy of preimplantation genetic screening to increase ongoing pregnancy rates in couples without known genetic disorders. METHODS: Systematic review and meta-analysis of randomized controlled trials. Two reviewers independently determined study eligibility and extracted data. RESULTS: Ten randomized trials (1,512 women) were included. The quality of evidence was moderate. Meta-analyses using a random-effects model suggest that PGS has a lower rate of ongoing pregnancies (risk ratio=0.73, 95% confidence interval 0.62-0.87) and a lower rate of live births (risk ratio=0.76, 95% confidence interval 0.64-0.91) than standard in vitro fertilization/intracytoplasmic sperm injection. CONCLUSIONS: In women with poor prognosis or in general in vitro fertilization program, in vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic screening for aneuploidy does not increase but instead was associated with lower rates of ongoing pregnancies and live births. The use of preimplantation genetic screening in daily practice does not appear to be justified.

Use of letrozole in assisted reproduction: a systematic review and meta-analysis.

BACKGROUND: Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis. METHODS: A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled. RESULTS: Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66-2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73-2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70-2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78-1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67-2.91). CONCLUSIONS: Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction.