Current Women's Health Reviews - Volume 6, Issue 3, 2010

The Special Issue on “Recent Advances in Reproductive Endocrinology and Women's Health” published by the Current Women's Health Reviews is a series of two volumes containing articles on cutting edge technology and contemporary topics of importance to reproductive endocrinologists, general gynecologists and specialists alike. The second volume has excellent articles on many recent advances and state-of-the-art technologies related to the field of assisted production and fertility preservation in women. Dr Kader et al. present recent updates on “Single Blastocyst Transfer: Contemporary Experience”. The authors state that the cryopreserved single blastocyst transfer has been developed as a practical method that can be used to optimize pregnancy outcomes following an unsuccessful initial transfer or in patients who do not meet initial transfer criteria. In their article on “The role of oxidative stress in assisted reproduction”, Drs. Gupta et al. explain that sperm and oocytes used in assisted reproductive techniques are subjected to oxidative stress because gametes lack the natural antioxidant defences that are present during in vivo reproduction in the male and female reproductive tract. In the past, studies quantified OS using inconvenient and labour-intensive biochemical methods to measure reactive oxygen species (ROS) and assess the antioxidant status within follicular fluid and culture fluid. Metabolomic profiling is a faster, more accurate method of quantifying OS during ART and may be used to identify gametes and embryos that are more likely to contribute to successful implantation and pregnancy. Various studies on the benefits of oral antioxidant supplementation in male and female patients undergoing ART procedures have yielded inconsistent and conflicting reports, and further research is required. Dr Ahmady et al. from the Macdonald IVF and Fertility program discuss pre-implantation and prenatal testing techniques that provide genetic information and detect birth defects or abnormalities in an embryo/fetus before implantation/birth. They emphasize that the limitations of FISH and PCR will lead to the use of whole-genome analysis/CGH in the setting of in vitro fertilization (IVF), replacing current PGD testing. Its preliminary application has been encouraging as more chromosomes can be analyzed with higher sensitivity and accuracy. Dr Aboulghar et al. from the The Egyptian IVF Center have contributed an excellent article on “coasting,” which is a popular method of preventing ovarian hyperstimulation syndrome (OHSS). The authors point out that while coasting does not totally avoid the risk of OHSS, it decreases its incidence in high-risk patients. They highlight the effectiveness of coasting in patients undergoing intracytoplasmic sperm injection (ICSI) and the fact that it does not jeopardize outcomes. Coasting for >3 days is associated with a moderate decrease in pregnancy rates. The authors state that coasting is a feasible option in patients undergoing IVF cycles with GnRH antagonists. Dr Gardner et al. have contributed an excellent article that discusses state-of-the-art technologies such as metabolomics and their application in the ART field. The authors have stated that metabolomics technology is perceived as an important diagnostic tool in clinical IVF that has the potential to assess embryo viability prior to transfer or cryopreservation. The authors conclude that as an embryo selection technique, metabolomics screening will form an integral part of ART laboratories. This will lead to an enhanced ability to determine the functional metabolic phenotype of an embryo as a key indicator of viability. They also highlight that the affordability of the new techniques is likely to improve as they become more readily available and tailored to clinical IVF and as they integrate with other cost effective and efficient technologies such as chip-based analysis. This special issue also contains 4 articles on fertility preservation by researchers from Cleveland Clinic, the University of Toledo and University Hospital-Case Western Reserve University. The article on the economics of female fertility preservation discusses the increasing demand of fertility preservation and obstacles that hinder the creation of a standard of care. The authors analyze the challenges to establishing higher quality care standards and provide suggestions for continued research and multidisciplinary collaboration for a larger patient population....

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Embryo implantation depends on both embryo quality and the endometrial environment. Implantation failure has a complex, variable pathophysiology and is detrimental to the outcome of in vitro fertilization (IVF). Thus, patients with multiple implantation failure require an individualized approach to diagnosing and managing treatment options for future IVF cycles. These options should be based on concrete, unambiguous, consistent scientific evidence with randomized, controlled trials. We review and discuss 14 treatment options: (i) blastocyst transfer, (ii) assisted hatching, (iii) co-culture, (iv) preimplantation genetic screening, (v) hysteroscopy, (vi) sildenafil, (vii) salpingectomy for tubal disease, (viii) oocyte donation, (ix) transfer of six or more embryos, (x), intratubal embryo transfer, (xi) natural cycle IVF, (xii) antiphospholipid antibodies (APA) testing and treatment, (xiii) allogenic lymphocyte therapy, and (xiv) IV immunoglobin therapy. The approaches were evaluated based on available information from studies, expert opinions, consensus, etc. We conclude that blastocyst transfer, assisted hatching, salpingectomy for tubal disease, and hysteroscopy in IVF procedures are clinically effective. This review serves as a summary of current treatment options for clinicians to counsel patients and manage their expectations based on strong and reliable evidence.

Recent studies demonstrated an overwhelming success in single blastocyst transfer (SBT): implantation rates (IR) were 60.9%-70.5% and pregnancy rates (PR) were 60.9%-76% while the multiple pregnancy rates (MPR) were 0%-3.2%. Most of these studies involved good prognosis patients not more than 37 years of age. The results indicated that SBT decreased the number of multiple pregnancies while maintaining desirable pregnancy outcomes. However, SBT and cryopreserved single blastocyst transfer (cSBT) in the field of in vitro fertilization (IVF) are still in their infancy. Guidelines for the number of blastocysts being transferred and the techniques have not yet been standardized. The method to estimate the most viable blastocyst has not yet been proposed. The success of SBT also was found to be highly associated with the technique and patients' and clinicians' perceptions toward it.

Aim: Oxidative stress contributes to the high rate of failure seen in assisted reproductive techniques in achieving fertilization and pregnancy. Many studies have been done to elucidate the sources of oxidative stress in the setting of assisted reproductive technology (ART) and interventions to overcome its negative influence on the outcome of IVF and ICSI. This article explores the utility of metabolomics as a novel, non-invasive method of accurately and efficiently quantifying oxidative stress. The aim of this study was to review the current literature on the effects of various interventions, including the use of antioxidants supplementation of IVF culture media and patients to improve fertilization and pregnancy rates in subfertile patients undergoing ART. Methods: Review of recent publications through Pubmed and the Cochrane data base. Results: Oxidative stress is correlated with negatives ART outcomes. Both exogenous and endogenous sources of reactive oxygen species during IVF/ICSI are well established in the literature. Compared to IVF, ICSI is known to minimize the exposure of gametes to endogenous sources of oxidative stress. Strategies to control exogenous sources of oxidative stress within the ART setting include reducing visible/near UV light exposure, the addition of metal chelators to culture media, maintenance of low oxygen tension in the environment and the use of antioxidant therapy. Antioxidant supplementation of culture media with vitamin C, vitamin E, and melatonin has been investigated and yielded conflicting results. Whereas oral antioxidant supplementation of male patients has been accepted and is currently practiced, there is a lack of consensus regarding the effectiveness of supplementation of vitamin C, vitamin E and melatonin in females undergoing ART. Conclusion: There is a need for further investigation with randomized controlled studies to confirm the efficacy and safety of antioxidant supplementation of culture media and patients as well as the need to determine the dosage required to improve fertilization rates and pregnancy outcome with IVF/ICSI.

The objective of this article is to review the current literature on the value of coasting for the prevention of ovarian hyperstimulation syndrome (OHSS). Coasting is a common procedure that is performed in ovarian stimulation cycles at risk of OHSS. Coasting is done by stopping FSH injections and monitoring E2 daily until it drops below 3000 pg/mL then hCG is given. Depriving granulosa cells of the FSH stimulus results in their apoptosis, thus reducing levels of E2 and vascular endothelial growth factor (VEGF linked to the pathogenesis of OHSS). Meanwhile, the small follicles that are dependent on FSH will undergo atresia, while large follicles will not be affected. Coasting is effective in reducing the OHSS rate, but complete prevention is not possible. Prolonged coasting is associated with a significantly lower pregnancy rate.

Pre-implantation and prenatal testing provide genetic information and detect birth defects or abnormalities in an embryo/fetus before implantation/born. In this review, the process and details of the two testing are discussed.

Multiple pregnancies have been and remain the most common and serious complication of assisted reproductive technologies (ART). Prematurity is the major complication of multiple pregnancies although there are other problems affecting the children and parents also increase significantly. The scope of the problem of ART and multiple pregnancies is discussed as well as the specific issues involving children and parents. Progress in decreasing ART multiple pregnancies and suggested steps to further decrease ART multiple pregnancies are also discussed.

Along with standard morphological indicators of preimplantation embryo development, information gained from novel “Omics” platforms is providing more detailed functional characterizations of embryo phenotype. Since embryo metabolism is a critical driver of development and implantation, it is proposed that analysis of the embryo metabolome may reveal several physiologically relevant markers. Metabolomics analysis is currently showing significant promise in this context, providing a systematic method of screening for low molecular weight metabolic by-products, in isolated cell extracts and biological fluids. Correlations between in vitro development and pregnancy outcomes have already been described after retrospective data comparison with metabolomic profiles. This article summarizes progress and current findings of metabolomic analysis as a new and complimentary technology for screening embryo cohorts in clinical IVF, to facilitate prognostic selection of a single embryo for transfer.

Fertility preservation options for women are currently only routinely offered to patients who face iatrogenic fertility loss, and most options are considered experimental. The most common modalities for female fertility preservation are embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation, the later two of which remain in the experimental arena. Natural fertility loss is affecting women as significantly as premature fertility loss. Increasing cancer survival and the modern reproductive trend of delaying childbearing are indications for the need and demand for fertility preservation. Advances in the field are necessary to respond to this demand and include superior cryopreservation techniques and fertility preservation technologies, customized guidelines, comprehensive care plans, and availability of more cost-efficient procedures. The obstacles to creating a standard of care for fertility preservation are as broad as the field itself. Lack of patient awareness, limited physician experience and knowledge, inadequate counseling, costs, and ethical issues are some examples of the many challenges to establishing a standard of care. With continued research and multidisciplinary collaboration, a higher quality of care may be provided to a larger patient population who wishes to maximize their fertility potential in the future.

The existing quantity of follicles and their response to stimulation at a particular age predicts the ovarian reserve. In vitro fertilization is emerging as a common method of treatment of infertility. This technique is not 100% accurate and puts the patient and the couple in both physical and financial burden. It is important to predict the outcome of a cycle of IVF to counsel a patient prior to proceeding. The ovarian reserve is the main functional component which might guide the outcome. There may be many factors affecting ovarian reserve but the age of the patient is the most important one. Various markers have been utilized to determine ovarian reserve in women which are endocrine, radiological or dynamic tests. No perfect marker has been identified yet but some have proven to be better than the other. This review will discuss the different methods of testing ovarian reserve and the current research that might help the clinician to predict outcome prior to initiating IVF.

Ovarian transplantation may be the future of fertility preservation. Although ovarian fragments graft is known to restore fertility, but a large number of primordial follicles are lost during the neo vacularisation period and the life span of the transplant is usually short. Whole ovary transplantation may restore ovarian function immediately and during long time. Nevertheless results of whole transplantation are still disappointing. Only one gestation in animal had been reported.

A wide variety of fertility preservation options in women is available; however, most of the currently available strategies are still experimental and do not guarantee subsequent fertility. The only established method is in vitro fertilization with embryo cryopreservation prior to cancer therapy. Other proposed strategies to preserve fertility in women with cancer include: storage of frozen ovarian tissue or the whole ovary for future transplantation, storage isolated follicles for in vitro growth and maturation and ovarian transposition before radiotherapy. The effectiveness of ovarian protection during chemotherapy with GnRH analogs is yet to be shown.