Free Access Articles
Fertility preservation during the COVID-19 pandemic: mitigating the viral contamination risk to reproductive cells in cryostorage
Reopening fertility care services across the world in the midst of a pandemic brings with it numerous concerns that need immediate addressing, such as the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the male and female reproductive cells and the plausible risk of cross-contamination and transmission. Due to the novelty of the disease the literature contains few reports confirming an association of SARS-CoV-2 with reproductive tissues, gametes and embryos. Cryobanking, an essential service in fertility preservation, carries the risk of cross-contamination through cryogenic medium and thus calls for risk-mitigation strategies.Is there an association between oocyte number and embryo quality? A systematic review and meta-analysis
The aim of assisted reproduction technology (ART) is to help an infertile couple have a healthy baby born at term. Multifollicular growth induced by ovarian stimulation can lead to the collection of multiple oocytes, which, in turn, seems to increase pregnancy chances after ART. Hence, clinicians have for years been trying to obtain an adequate number of oocytes while minimizing the risk of ovarian hyperstimulation syndrome. Some have advocated that a higher number of collected oocytes is associated with improved outcomes (Baker et al., 2015; Macklon et al., 2006; van der Gaast et al., 2006).GLP-1 receptor agonists versus metformin in PCOS: a systematic review and meta-analysis
This meta-analysis aimed to evaluate the efficacy and safety of glucagon-like peptide 1 (GLP-1) receptor agonists for women with polycystic ovary syndrome (PCOS) by comparing their effect with that of metformin. Electronic databases (PubMed, EMBASE, Cochrane Library, WanFang Database, CNKI) dating from their establishment to June 2018 were searched to find all randomized controlled trials (RCTs) reporting the efficacy of GLP-1 receptor agonists versus metformin for patients with PCOS. Therapeutic variables included menstrual cycle, sex hormone and clinical manifestations, glucose metabolism and other metabolic indexes.Use of progestins to inhibit spontaneous ovulation during ovarian stimulation: the beginning of a new era?
Advances in oocyte and embryo cryopreservation for assisted reproduction prompted new approaches to ovarian stimulation. Attention has been paid to progesterone and its derivatives to block the LH surge, as oocyte vitrification removes possible harmful effects of progestins on endometrial receptivity. This review summarizes the current status of progestin use to inhibit ovulation during ovarian stimulation compared with conventional ovarian stimulation. Progestin-primed ovarian stimulation is shown to effectively inhibit spontaneous ovulation, without affecting the number of retrieved oocytes and embryo quality.A meta-analysis of pregnancy-related outcomes and complications in women with polycystic ovary syndrome undergoing IVF
Polycystic ovary syndrome (PCOS) is one of the most common and complex hormonal disorders seen in women and is considered to be a significant public health issue (Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group, 2004). PCOS has a negative effect on women's health across the lifespan, leading to, for example, anxiety, depression, insulin resistance, abdominal obesity, hypertension and dyslipidaemia (Teede et al., 2010); it is also an important cause of infertility in women of reproductive age because of the associated anovulation (Homburg and Crawford, 2014).Influence of oral vitamin and mineral supplementation on male infertility: a meta-analysis and systematic review
This meta-analysis and systematic review investigated evidence of the effect of oral micronutrient supplementation on male fertility. Following searches of PubMed, Ovid/Ovid Medline(r) and Embase, 18 randomized, double-blind, placebo-controlled trials were included in the meta-analysis (seven studies) and/or the systematic review (12 studies). The meta-analysis showed significant improvement in semen parameters for selenium (200µg/day and 100µg/day) (standard mean difference [SMD] 0.64 for oligozoospermia, 1.39 for asthenozoospermia), L-carnitine (2 g/day) and acetyl-L-carnitine (LAC; 1 g/day) combined (SMD 0.57 for asthenozoospermia), and co-enzyme Q10 (200 and 300 mg/day) (SMD 0.95 for oligozoospermia, 1.48 for asthenozoospermia, 0.63 for teratozoospermia).Imaging the ovary
Using mainly histological analyses of fixed ovarian tissues and ultrasound imaging of ovaries in vivo, earlier imaging studies have established the basic framework of ovarian folliculogenesis as well as luteal formation and regression. The ovary contains individual follicles as functional structures, together with corpora lutea, interstitial tissues, innermost medulla and the outmost layer of the surface epithelium. Most of the 800,000 primordial follicles found at birth in human females remain at the dormant stage.Can time-lapse parameters predict embryo ploidy? A systematic review
Embryo morphology assessment performs relatively poorly in predicting implantation. Embryo aneuploidy screening (PGS) has recently improved, but its clinical value is still debated, and the development of a cheap non-invasive method for the assessment of embryo ploidy status is a highly desirable goal. The growing implementation of time-lapse devices led some teams to test the effectiveness of morphokinetic parameters as predictors of embryo ploidy, with conflicting results. The aim of this study was to conduct a comprehensive review of the literature on the predictive value of morphokinetic parameters for embryo ploidy status.Multiple pregnancies achieved with IVF/ICSI and risk of specific congenital malformations: a meta-analysis of cohort studies
Studies comparing risk of specific congenital malformations (CM) between multiple pregnancies resulting from IVF/intracytoplasmic sperm injection (ICSI) and those conceived naturally report conflicting results; furthermore, there is a lack of a complete overview. This meta-analysis aimed to address which types of CM are increased in IVF/ICSI multiple pregnancies compared with those conceived naturally. All studies testing the association between IVF/ICSI multiple pregnancies and specific CM identified in various databases were considered.Effect of male body mass index on assisted reproduction treatment outcome: an updated systematic review and meta-analysis
Men with a body mass index (BMI) of 30 or over are more likely to have reduced fertility and fecundity rates. This systematic review and meta-analysis evaluated the effect of male BMI on IVF and intracytoplasmic sperm injection (ICSI) outcome. An electronic search for published literature was conducted in MEDLINE and EMBASE between 1966 and November 2016. Outcome measures were clinical pregnancy rates (CPR) and live birth rates (LBR) per IVF or ICSI cycle. Eleven studies were identified, including 14,372 cycles; nine reported CPR and seven reported LBR.Follicular flushing in patients with poor ovarian response: a systematic review and meta-analysis
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, I2 = 70%; P = 0.21; three RCT, n = 210).A search for molecular mechanisms underlying male idiopathic infertility
Infertility affects approximately 15% of the couples wanting to conceive. In 30 − 40% of the cases the aetiology of male infertility remains unknown and is called idiopathic male infertility. When assisted reproductive technologies are used to obtain pregnancy, an adequate (epi)genetic diagnosis of male infertility is of major importance to evaluate if a genetic abnormality will be transmitted to the offspring. In addition, there is need for better diagnostic seminal biomarkers to assess the success rates of these assisted reproductive technologies.Role of Withania somnifera (Ashwagandha) in the management of male infertility
To manage male infertility caused by hormonal imbalance, infections and other predicaments, multifarious treatment strategies are emerging worldwide. Contemporary treatments, such as assisted reproductive techniques, are costly with low success rates of only 10–30%; however, herbal remedies are gaining more attention as an alternative or supplementary therapeutic modality for male infertility. The beneficial effects induced by oral intake of the roots of a small evergreen shrub, Withania sominifera (Ashwagandha) on semen quality of infertile men have previously been studied.Risk of pelvic inflammatory disease after intrauterine insemination: a systematic review
The aim of this study was to ascertain the incidence of pelvic inflammatory disease (PID) after intrauterine insemination (IUI). A systematic review was conducted using three different approaches: a search of IUI registries; a search of published meta-analyses; and a search of prospective randomized trials. Search terms were ‘IUI’, ‘complications’, ‘infection’ and ‘PID’. Two IUI registers were identified that met the inclusion criteria, totalling 365,874 cycles, with 57 PID cases being reported.Progress in the diagnosis and management of adolescent endometriosis: an opinion
Until recently, adolescent endometriosis has been considered a rare, often transient, condition not particularly serious for the young patient. Against this background, and not without disagreement by some, we have pointed out that early onset endometriosis (EOE) may at times be severe, necessitating quick diagnosis and proper treatment (Brosens et al., 2013b, 2014). To substantiate this viewpoint, we carefully searched published research, including some early paediatric research, and identified peritoneal reflux from neonatal uterine bleeding (NUB) occurring in 3–5% of female neonates, as a biologically plausible and likely cause of EOE (Brosens and Benagiano, 2013, 2016; Brosens et al., 2013a; Gargett et al., 2014).Insights from clinical experience in treating IVF poor responders
‘Poor responders’ is a term used to describe a subpopulation of IVF patients who do not respond well to ovarian stimulation with gonadotrophins. While there is no standard definition of a poor responder, these patients tend to be of advanced maternal age (≥40 years), have a history of poor ovarian response with conventional stimulation protocols, and/or have low ovarian reserve. Despite the heterogeneity of this patient group, there are characteristics and needs common to many poor responders that can be addressed through a holistic approach.Perinatal outcomes after stimulated versus natural cycle IVF: a systematic review and meta-analysis
Pregnancies resulting from assisted reproductive techniques are at higher risk of adverse perinatal outcomes compared with spontaneous conceptions. Underlying infertility and IVF procedures have been linked to adverse perinatal outcomes. It is important to know if ovarian stimulation influences perinatal outcomes after IVF. A systematic search for relevant studies was conducted up to November 2016 on the following databases: PubMed, EMBASE, DARE and Cochrane Central Register of Controlled Trials.Paving the way for a gold standard of care for infertility treatment: improving outcomes through standardization of laboratory procedures
Infertility affects over 70 million couples globally. Access to, and interest in, assisted reproductive technologies is growing worldwide, with more couples seeking medical intervention to conceive, in particular by IVF. Despite numerous advances in IVF techniques since its first success in 1978, almost half of the patients treated remain childless. The multifactorial nature of IVF treatment means that success is dependent on many variables. Therefore, it is important to examine how each variable can be optimized to achieve the best possible outcomes for patients.Inositol supplementation in women with polycystic ovary syndrome undergoing intracytoplasmic sperm injection: a systematic review and meta-analysis of randomized controlled trials
Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disease that involves menstrual dysfunction and reproductive difficulty, as well as metabolic problems. Use of the Rotterdam criteria will probably increase its already high prevalence, and currently, it is the most common endocrinopathy in women, affecting 7–14% of women of childbearing age worldwide (Bozdag et al., 2016).Pathogenesis of adenomyosis: an update on molecular mechanisms
Adenomyosis is a uterine disorder becoming more commonly diagnosed in women of reproductive age because of diagnostic imaging advancements. The new epidemiological scenario and the clinical evidence of pelvic pain, abnormal uterine bleeding and infertility are changing the classic perspective of adenomyosis as a premenopausal disease. In the last decade, the evaluation of multiple molecular mediators has improved our knowledge of pathogenic mechanisms of adenomyosis, supporting that this is an independent disease from endometriosis.‘Money for nothing’. The role of robotic-assisted laparoscopy for the treatment of endometriosis
During the last decades, laparoscopic surgery has been accepted as the technique of choice for the treatment of endometriosis, because it provides long-term outcomes comparable to those achieved by laparotomy, with the established advantages of a minimally invasive technique, including better visualization, shorter hospital stay, faster recovery and better cosmetic results (Adamson et al., 1992; Daraï et al., 2010; Luciano et al., 1992; Vercellini et al., 2003).Anti-Müllerian hormone kinetics in pregnancy and post-partum: a systematic review
The aim of this systematic review is to critically appraise the available evidence regarding the kinetics of anti-Müllerian hormone (AMH) during pregnancy and post-partum. A systematic literature search was conducted in MEDLINE, Embase, CENTRAL, Scopus and Web of Science on 14 December 2015, aiming to identify studies providing data on the serum concentration of AMH in women at various stages of gestation and post-partum. There was a total of 1719 participants across eight studies. Seven out of the eight studies reported a decline in serum AMH concentration with advancing gestational age.Ovarian stimulation protocols for IVF: is more better than less?
Conventional ovarian stimulation protocols for IVF are designed to achieve maximum oocyte yields. Conventional protocols, however, are associated with patient discomfort, increased risk of ovarian hyperstimulation syndrome and higher costs. In recent years, mild stimulation protocols have risen in popularity. These protocols typically use lower doses (≤150 IU/day), shorter duration of exogenous gonadotrophins, or both, compared with conventional protocols, with the goal of limiting the number of retrieved oocytes to less than eight.Effect of progesterone elevation in follicular phase of IVF-cycles on the endometrial receptivity
The premature rise of progesterone during the late follicular phase in stimulated IVF cycles is a frequent event, and emerging evidence shows that premature progesterone rise does negatively affect the outcome of assisted reproductive techniques. The effect of elevated peripheral progesterone levels in the late follicular phase seems to be on the endometrium and the window of implantation, which may lead to asynchrony between the endometrium and the developing embryo. In stimulated cycles, endometrial maturation is advanced on the day of oocyte retrieval, and patients with a progesterone level above 1.5 ng/ml on the day of final oocyte maturation have different endometrial gene expression profiles.Multiple-dose and double-dose versus single-dose administration of methotrexate for the treatment of ectopic pregnancy: a systematic review and meta-analysis
In this systematic review and meta-analysis, the effectiveness and safety among different dosage of methotrexate protocols for the treatment of unruptured tubal ectopic pregnancy was evaluated. Six studies of randomized contorlled trials were identified through searches conducted on PubMed, Embase and Cochrane Library between January 1974 and March 2016. The overall success rate of multiple-dose protocol was similar to the single-dose protocol (RR 1.07, 95% CI 0.99 to 1.17, I2 = 0%). The difference between double-dose and single-dose groups was not significant (RR 1.09, 95% CI 0.98 and 1.20, I2 = 0%).
