Category Archives: Human Reproduction

BACKGROUND

Vitrification is now a commonly applied technique for cryopreservation in assisted reproductive technology (ART) replacing, in many cases, conventional slow cooling methodology. This review examines evidence relevant to comparison of the two approaches applied to human oocytes and embryos at different developmental stages.

METHODS

Critical review of the published literature using PubMed with particular emphasis on studies which include data on survival and implantation rates, data from fresh control groups and evaluation of the two approaches in a single setting.

RESULTS

Slow cooling is associated with lower survival rates and compromised development relative to vitrification when applied to metaphase II (MII) oocytes, although the vitrification results have predominantly been obtained using direct contact with liquid nitrogen and there is some evidence that optimal protocols for slow cooling of MII oocytes are yet to be established. There are no prospective randomized controlled trials (RCTs) which support the use of either technique with pronuclear oocytes although vitrification has become the method of choice. Optimal slow cooling, using modifications of traditional methodology, and vitrification can result in high survival rates of early embryos, which implant at the same rate as equivalent fresh counterparts. Many studies report high survival and implantation rates following vitrification of blastocysts. Although slow cooling of blastocysts has been reported to be inferior in some studies, others comparing the two approaches in the same clinical setting have demonstrated comparable results. The variation in the extent of embryo selection applied in studies can lead to apparent differences in clinical efficiency, which may not be significant if expressed on a ‘per oocyte used’ basis.

CONCLUSIONS

Available evidence suggests that vitrification is the current method of choice when cryopreserving MII oocytes. Early cleavage stage embryos can be cryopreserved with equal success using slow cooling and vitrification. Successful blastocyst cryopreservation may be more consistently achieved with vitrification but optimal slow cooling can produce similar results. There are key limitations associated with the available evidence base, including a paucity of RCTs, limited reporting of live birth outcomes and limited reporting of detail which would allow assessment of the impact of differences in female age. While vitrification has a clear role in ART, we support continued research to establish optimal slow cooling methods which may assist in alleviating concerns over safety issues, such as storage, transport and the use of very high cryoprotectant concentrations.

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BACKGROUND

Chemotherapy treatment in premenopausal women is associated with an increased risk of premature ovarian failure (POF) but the exact mechanism through which this occurs is uncertain. In this review we examine the current evidence for the direct action of chemotherapeutic agents on the ovary and discuss possible molecular pathways through which follicle loss may occur.

METHODS

A systemic search of the databases, PubMed and Google Scholar, was made for all English language articles through to 2011 in each subject area discussed.

RESULTS

POF results from the loss of primordial follicles but this is not necessarily a direct effect of the chemotherapeutic agents. Instead, the disappearance of primordial follicles could be due to an increased rate of growth initiation to replace damaged developing follicles. Likewise, the loss of oocytes need not necessarily be a direct result of damage: evidence suggests that chemotherapy drugs can also induce oocyte death indirectly via damage to somatic cells. Specific molecular mechanisms and likely ovarian targets are discussed for some of the anti-cancer drugs most commonly used to treat premenopausal women. Finally, we consider current and prospective methods of preserving fertility.

CONCLUSIONS

It is likely that different chemotherapeutic drugs act through a range of mechanisms and on different target cells. More research into the cellular mechanisms underpinning chemotherapy-induced follicle loss could lead to the generation of treatments specifically designed to prevent POF.

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BACKGROUND

Threatened miscarriage is very common in early pregnancy. Chinese medicines have been widely used to prevent spontaneous pregnancy loss. However, the safety of Chinese medicines is still unknown. A systematic review was performed to identify and describe adverse events of Chinese medicines used for threatened miscarriage.

METHODS

Clinical studies of Chinese medicines for threatened miscarriage were selected. Primary outcomes were occurrence of adverse effects or toxicity of Chinese medicines. Secondary outcomes were failure of treatment and adverse pregnancy and perinatal outcomes.

RESULTS

Thirty-two relevant articles included 9 randomized controlled trials, 1 quasi-randomized controlled trial and 2 controlled trials comparing Chinese medicines alone or combined medicines with pharmaceuticals and 20 case series with no controls. Sample sizes of each study were generally small. There was variation in Chinese medicine formulation, dosage and duration of treatment. In the pooled randomized controlled trials, dry mouth, constipation and insomnia (2–10%) and intervention failure (3.1–22.3%), diabetic complications (3%), preterm delivery (5%) and neurodevelopmental morbidity (1.8%) were recorded. Meta-analysis demonstrated that intervention failure was significantly lower in the combined Chinese medicines groups than in the Western medicines controls (relative risk = 0.46; 95% confidence interval: 0.30–0.70, I²= 0%). No significant differences were found between these groups for adverse effects and toxicity or for adverse pregnancy and perinatal outcomes.

CONCLUSIONS

Studies varied considerably in design, interventions and outcome measures, therefore conclusive results remain elusive. In the absence of placebo-controlled trials, the safety of Chinese medicines for the treatment of threatened miscarriage is unknown. Rigorous scientific and clinical studies to assess the possible risks of Chinese medicines are needed.

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BACKGROUND

Earlier reviews have suggested that IVF/ICSI pregnancies are associated with higher risks. However, there have been recent advances in the way IVF/ICSI is done, leading to some controversy as to whether IVF/ICSI singletons are associated with higher perinatal risks. The objective of this systematic review was to provide an up-to-date comparison of obstetric and perinatal outcomes of the singletons born after IVF/ICSI and compare them with those of spontaneous conceptions.

METHODS

Extensive searches were done by two authors. The protocol was agreed a priori. PRISMA guidance was followed. The data were extracted in 2 x 2 tables. Risk ratio and risk difference were calculated on pooled data using Rev Man 5.1. Quality assessment of studies was performed using Critical Appraisal Skills programme. Sensitivity analysis was performed when the heterogeneity was high (I² > 50%).

RESULTS

There were 20 matched cohort studies and 10 unmatched cohort studies included in this review. IVF/ICSI singleton pregnancies were associated with a higher risk (95% confidence interval) of ante-partum haemorrhage (2.49, 2.30–2.69), congenital anomalies (1.67, 1.33–2.09), hypertensive disorders of pregnancy (1.49, 1.39–1.59), preterm rupture of membranes (1.16, 1.07–1.26), Caesarean section (1.56, 1.51–1.60), low birthweight (1.65, 1.56–1.75), perinatal mortality (1.87, 1.48–2.37), preterm delivery (1.54, 1.47–1.62), gestational diabetes (1.48, 1.33–1.66), induction of labour (1.18, 1.10–1.28) and small for gestational age (1.39, 1.27–1.53).

CONCLUSIONS

Singletons pregnancies after IVF/ICSI are associated with higher risks of obstetric and perinatal complications when compared with spontaneous conception. Further research is needed to determine which aspect of assisted reproduction technology poses most risk and how this risk can be minimized.

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BACKGROUND

The functional reproductive alterations seen in women with type 1 diabetes (T1D) have changed as therapy has improved. Historically, patients with T1D and insufficient metabolic control exhibited a high prevalence of amenorrhea, hypogonadism and infertility. This paper reviews the impact of diabetes on the reproductive axis of female T1D patients treated with modern insulin therapy, with special attention to the mechanisms by which diabetes disrupts hypothalamic–pituitary–ovarian function, as documented mainly by animal model studies.

METHODS

A comprehensive MEDLINE search of articles published from 1966 to 2012 was performed. Animal model studies on experimental diabetes and human studies on T1D were examined and cross-referenced with terms that referred to different aspects of the gonadotropic axis, gonadotrophins and gonadal steroids.

RESULTS

Recent studies have shown that women with T1D still display delayed puberty and menarche, menstrual irregularities (especially oligomenorrhoea), mild hyperandrogenism, polycystic ovarian syndrome, fewer live born children and possibly earlier menopause. Animal models have helped us to decipher the underlying basis of these conditions and have highlighted the variable contributions of defective leptin, insulin and kisspeptin signalling to the mechanisms of perturbed reproduction in T1D.

CONCLUSIONS

Despite improvements in insulin therapy, T1D patients still suffer many reproductive problems that warrant specific diagnoses and therapeutic management. Similar to other states of metabolic stress, T1D represents a challenge to the correct functioning of the reproductive axis.

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BACKGROUND

Disruption of ovulation occurs in different types of clinical infertility. The World Health Organization (WHO) has provided a classification of ovulation disorders. This review focuses on WHO group 2 anovulation.

METHODS

Searches were performed in Medline/PubMed and EMBASE. Each subject summary was presented to the European Society of Human Reproduction and Embryology (ESHRE) Workshop Group, where omissions or disagreements were resolved by discussion.

RESULTS

Disorders resulting in ovulatory disturbances are a relatively common cause of infertility. They occur most frequently in the context of WHO group 2 anovulation as reflected, for example, in the polycystic ovary syndrome (PCOS). The aetiology of PCOS remains unclear but evidence exists for a multifactorial origin with a genetic predisposition. Women with PCOS show an increased time to pregnancy but their eventual family size is not necessarily reduced. Also their frequency of miscarriage does not appear increased. Clomiphene citrate is still the first-line treatment in subfertile anovulatory patients with PCOS, with gonadotrophins and laparoscopic ovarian surgery as second-line options. Aromatase inhibitors show promising results.

CONCLUSIONS

Long-term health risks in patients with WHO group 2 anovulation demand their general health be monitored, even after their reproductive needs have been fulfilled. Metabolic and cardiovascular risk prevention in women with PCOS should start as early as possible. It is not easy to analyse the possible role of PCOS, independent of obesity, metabolic syndrome, insulin resistance and diabetes, on long-term health.

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http://humupd.oxfordjournals.org/rss/current.xml