[Show abstract][Hide abstract] ABSTRACT: Simultaneous transfer of multiple embryos in an assisted reproductive technology (ART) cycle results in a high rate of multiple pregnancy. Besides the medical complications associated with multiple pregnancy, the financial burden of the resultant preterm infants is also substantial. The current review evaluates the costs associated with the care of preterm infants that are born as a result of ART-associated multiple pregnancies.
In 2006, 30% of all ART live births were multiple infant deliveries in the USA. This resulted in 48% of all ART neonates being the product of a multiple infant delivery. In the same year, 62% of ART twins and 97% of ART triplets were delivered preterm, corresponding to approximately 17 000 infants. The Board of Health Sciences Policy has estimated the mean cost of each preterm infant to be US$ 51 600. Therefore, the financial burden of ART-associated preterm deliveries is estimated to be approximately US$ 1 billion annually. This figure has remained essentially unchanged between 2001 and 2006, despite decreasing number of embryos transferred, due to increasing total number of ART cycles performed.
Preterm deliveries that result from ART-associated multiple pregnancies add a substantial burden to overall US healthcare expenditure annually. Policies limiting the number of embryos transferred should be considered with a perspective to increase elective single embryo transfers.
Full-text · Article · Mar 2011 · Current opinion in obstetrics & gynecology
[Show abstract][Hide abstract] ABSTRACT: To compare the impact of mandated IVF insurance coverage on ET practices and resulting multiple pregnancy rates.
Retrospective analysis of all fresh, nondonor IVF cycles performed in the United States in 2006.
A total of 91,753 fresh, nondonor IVF cycles in the United States.
Pregnancy rate, live-birth rate, embryos transferred, multiple pregnancy rate.
Overall, nonmandated states had a significantly higher pregnancy rate (38.8% vs. 35%) and live-birth rate (32.2% vs. 29.1%) than mandated states. Nonmandated states also had a significantly higher twin rate (28.1% vs. 26%) and triplet rate (3.9% vs. 3.4%). The average number of embryos transferred was also significantly higher in nonmandated states (2.6 vs. 2.2). These findings were more pronounced in the <35 and 35-37 age groups.
In the last 8 years, despite a reduction in the average number of embryos transferred and multiple pregnancy rates, there is a continued association between mandated IVF coverage, the transfer of fewer embryos, and lower rates of multiple pregnancies and births, particularly in the younger age groups.
No preview · Article · Mar 2011 · Fertility and sterility
[Show abstract][Hide abstract] ABSTRACT: Introduction Patients with cancer who desire to preserve their future reproductive potential but require immediate gonadotoxic treatments (chemo and/or radiotherapy), are left with few options for fertility preservation. These options include: (a) cryopreservation of ovarian tissues as cortical strips; (b) dual cryopreservation of both ovarian cortical tissue and cryopreservation, after in vitro maturation, of immature oocytes extracted from the small antral follicles visible within the ovarian cortex at the time of the harvest; (c) cryopreservation of one whole ovary [1–9]. Each of these options is still considered experimental (thus requiring Institutional Review Board approval and patient's informed consent). Ovarian cryopreservation and transplantation [10–11], either as heterotopic or orthotopic allografts, has shown some reproductive success [12–14]. At the time of writing, a total of seven live births from re-transplantation of ovarian cortical tissue to an orthotopic location have been reported [15–19], while four more have been announced at a meeting, but not yet published. Typically, it takes about 4–5 months for resumption of endocrine function as evidenced by menses or serological hormonal evaluation. However, the re-transplanted cortical pieces only retain ovarian function for a short time and almost all ceased to function by 3 years [6, 20, 21]. There are several reasons to explain this transient return of ovarian function followed by the rapid decline. One reason is that the amount of cryopreserved/thawed cortical tissue re-transplanted during a graft is limited.
[Show abstract][Hide abstract] ABSTRACT: Diethylstilbestrol (DES) and bisphenol-A (BPA) are estrogen-like endocrine-disrupting chemicals that induce persistent epigenetic changes in the developing uterus. However, DES exposure in utero is also associated with an increased risk of breast cancer in adult women. Similarly, fetal exposure to BPA induces neoplastic changes in mammary tissue of mice. We hypothesized that epigenetic alterations would precede the increased risk of breast neoplasia after in utero exposure to endocrine disruptors. Enhancer of Zeste Homolog 2 (EZH2) is a histone methyltransferase that has been linked to breast cancer risk and epigenetic regulation of tumorigenesis. We examined the effect of BPA and DES on EZH2 expression and function in MCF-7 cells and in mammary glands of mice exposed in utero. DES and BPA treatment approximated human exposure. EZH2 functional activity was assessed by measuring histone H3 trimethylation. Treatment of MCF-7 cells with DES or BPA led to a 3- and 2-fold increase in EZH2 mRNA expression, respectively (p < 0.05) as well as increased EZH2 protein expression. Mice exposed to DES in utero showed a >2-fold increase in EZH2 expression in adult mammary tissue compared with controls (p < 0.05). EZH2 protein was elevated in mammary tissue of mice exposed to DES or BPA. Histone H3 trimethylation was increased in MCF-7 cells treated with BPA or DES. Similarly, mice exposed to BPA or DES in utero showed increased mammary histone H3 trimethylation. Developmental programming of EZH2 is a novel mechanism by which in utero exposure to endocrine disruptors leads to epigenetic regulation of the mammary gland.
Preview · Article · Jun 2010 · Hormones and Cancer
[Show abstract][Hide abstract] ABSTRACT: To investigate the oocyte-to-baby rate when controlled ovarian stimulation was performed on a highly successful donor population and to evaluate whether they produce a higher proportion of reproductively competent oocytes compared with standard donors.
Retrospective analysis of clinical and embryological database.
A total of 191 oocyte donation cycles were analyzed from 53 donors (28 best-prognosis donors and 23 standard donors).
Total number of oocytes collected, the number of embryos transferable (fresh and frozen). and corresponding oocyte to live baby born (LBB) rates. In patients with remaining frozen embryos, the final LBB rate was estimated according to our reported rates.
A total of 130 oocyte retrievals from the best-prognosis donors yielded 2,470 oocytes. The total LBB per oocyte retrieved and LBB per embryo transferred was 7.3% and 24.6%, respectively. A total of 61 oocyte retrievals from the standard donors yielded 1,044 oocytes. The total LBB per oocyte and LBB per embryo transferred was 5.0% and 16.6%, respectively. This is significantly different from the best-prognosis donor group. Success rates were also analyzed after grouping donors based on the number of oocytes retrieved per cycle. In the best-prognosis group, the oocyte use rate increased significantly when fewer oocytes were retrieved, whereas the oocyte-to-baby rate was similar regardless of the number of oocytes for the standard donor group.
This retrospective analysis revealed the existence of a subset of good-prognosis donors who produce a higher oocyte-to-baby rate that is indicative of a more biologically efficient reproductive system. Their identification, albeit a posteriori, has clinical implications for safety, by reducing ovarian hyperstimulation syndrome and multiple pregnancies, as well as for assisted reproductive technology success.
No preview · Article · Mar 2010 · Fertility and sterility
[Show abstract][Hide abstract] ABSTRACT: Bisphenol-A (BPA) is a nonsteroidal estrogen that is ubiquitous in the environment. The homeobox gene Hoxa10 controls uterine organogenesis, and its expression is affected by in utero BPA exposure. We hypothesized that an epigenetic mechanism underlies BPA-mediated alterations in Hoxa10 expression. We analyzed the expression pattern and methylation profile of Hoxa10 after in utero BPA exposure. Pregnant CD-1 mice were treated with BPA (5 mg/kg IP) or vehicle control on d 9-16 of pregnancy. Hoxa10 mRNA and protein expression were increased by 25% in the reproductive tract of mice exposed in utero. Bisulfite sequencing revealed that cytosine-guanine dinucleotide methylation was decreased from 67 to 14% in the promoter and from 71 to 3% in the intron of Hoxa10 after in utero BPA exposure. Decreased DNA methylation led to an increase in binding of ER-alpha to the Hoxa10 ERE both in vitro as and in vivo as determined by EMSA and chromatin immunoprecipitation, respectively. Diminished methylation of the ERE-containing promoter sequence resulted in an increase in ERE-driven gene expression in reporter assays. We identify altered methylation as a novel mechanism of BPA-induced altered developmental programming. Permanent epigenetic alteration of ERE sensitivity to estrogen may be a general mechanism through which endocrine disruptors exert their action.
[Show abstract][Hide abstract] ABSTRACT: Introduction While previous chapters have focused on preservation of oocytes and embryos as well as ovarian tissue cortex, much progress has been made recently in the area of cryopreservation of the whole ovary. Patients who require immediate (within days) gonadotoxic therapy (whether chemo- or radiotherapy, or a combination of both) have few options for fertility preservation: (1) cryopreservation of ovarian tissues as cortical strips; (2) dual cryopreservation of both ovarian cortical tissue with cryopreservation and in vitro maturation of a few immature oocytes extracted from small follicles visible within the ovarian cortex; or (3) cryopreservation of one whole ovary. To date, ovarian cryopreservation and subsequent transplantation procedures, whether as heterotopic or orthotopic allografts, have been almost exclusively limited to avascular cortical pieces. Despite the careful use of cryoprotectants to prevent ice crystal formation at the time of freezing, the main drawback to cryopreservation of ovarian cortical strips is the ischemia that occurs at the time of transplantation. As these small cortical pieces are grafted without any vascular anastomosis, they are completely dependent for their survival on the speed at which neovascularization can be established after grafting. As this process requires a minimum of 7 days, the cells in the graft undergo significant ischemic damage, which results in massive loss of primordial follicles and, in turn, limits the lifespan of the graft. For a patient who desires long-term reproductive and endocrine function after transplantation, this method of fertility preservation may be suboptimal.
[Show abstract][Hide abstract] ABSTRACT: Infertile patients over the age of 40 are generally considered to have a low chance of success with assisted cycles despite high numbers of embryos transferred. The risk of multiple pregnancy in this group of patients is not well established. The present study determined the rate of embryos that fail to produce a live birth and the rate of multiple pregnancies in a cohort of women over the age of 40 undergoing IVF/intracytoplasmic sperm injection cycles, utilizing Society for Assisted Reproductive Technology reported cycle outcomes from national summaries as well as from two university-based IVF centres. The rate of embryo wastage for women over the age of 40 is approximately 95% and these women have a correspondingly low rate of multiple pregnancy per cycle started (2.5% and 1.6% for women aged 41-42 years and 43-44 years, respectively). These data underscore the low reproductive efficiency of oocytes in women over the age of 40 and the very low probability of a multiple-gestation live birth despite the high number of embryos transferred. This information is an important additional counselling tool at the time of embryo transfer in this group of patients.
No preview · Article · Dec 2009 · Reproductive biomedicine online
[Show abstract][Hide abstract] ABSTRACT: Recently, much progress has been made in the area of cryopreservation of ovarian tissue, one of the only options for fertility preservation available to women who require immediate gonadotoxic chemotherapy. Human ovarian cortical tissue strips have been cryopreserved, thawed, and autotransplanted with successful reproductive function. Cryopreservation of ovarian cortical strips, however, is limited by the ischemia that occurs at the time of retransplantation. Thus for patients that desire long-term resumption of endocrine function, cryopreservation of the whole ovary with an intact pedicle and vascular supply may be a better option. This article describes recent advances in whole ovary cryopreservation in both animal and human models, with a focus on surgical technique for removal, choice of cryoprotectants, freezing and thawing protocols, and preliminary results with organ retransplantation. Although no human cases of whole ovary retransplantation after cryopreservation have been performed to date, these preliminary studies have been encouraging, and it is likely that this option for fertility preservation will be a viable treatment option in the future.
No preview · Article · Nov 2009 · Seminars in Reproductive Medicine
[Show abstract][Hide abstract] ABSTRACT: Diethylstilbestrol (DES) is a nonsteroidal estrogen that induces developmental anomalies of the female reproductive tract. The homeobox gene HOXA10 controls uterine organogenesis, and its expression is altered after in utero DES exposure. We hypothesized that an epigenetic mechanism underlies DES-mediated alterations in HOXA10 expression. We analyzed the expression pattern and methylation profile of HOXA10 after DES exposure. Expression of HOXA10 is increased in human endometrial cells after DES exposure, whereas Hoxa10 expression is repressed and shifted caudally from its normal location in mice exposed in utero. Cytosine guanine dinucleotide methylation frequency in the Hoxa10 intron was higher in DES-exposed offspring compared with controls (P = 0.017). The methylation level of Hoxa10 was also higher in the caudal portion of the uterus after DES exposure at the promoter and intron (P < 0.01). These changes were accompanied by increased expression of DNA methyltransferases 1 and 3b. No changes in methylation were observed after in vitro or adult DES exposure. DES has a dual mechanism of action as an endocrine disruptor; DES functions as a classical estrogen and directly stimulates HOXA10 expression with short-term exposure, however, in utero exposure results in hypermethylation of the HOXA10 gene and long-term altered HOXA10 expression. We identify hypermethylation as a novel mechanism of DES-induced altered developmental programming.
[Show abstract][Hide abstract] ABSTRACT: In the last several decades, both the growing number of reproductive age cancer survivors, and the trend of women from western countries delaying child-bearing to a later age have been markedly increasing. The confluence of these two epidemiologic trends has led to the need for better and more widely available strategies for fertility preservation. In this paper, we will first review both the established and experimental methodologies which can be utilized for either the preservation or postponement of female fertility. These options currently include embryo and oocyte cryopreservation, cortical and whole ovary cryopreservation, ovarian transplantation, ovarian transposition, and gonadotropin releasing hormone agonist protection. As laboratory and surgical techniques for oocyte and ovary cryopreservation continue to improve, modalities now considered experimental will become part of routine practice for reproductive medicine specialists.