Effect Of Assisted Reproductive Technology Research Articles

Assisted Reproductive Technology, Congenital Malformations, and Epigenetic Disease

In the 3 decades since the birth of the first in vitro fertilization-conceived child, assisted reproduction technologies were rapidly assimilated into clinical care and are now responsible for 1% to 3% of all livebirths in North America and Europe. The rate of congenital anomalies is low (4% to 6%), though it represents a modest increase over the background rate of major malformations (3%). Additionally, emerging studies of imprinting and epigenetic conditions, those genetic disorders due to changes in DNA transcription without change in DNA sequence, suggest that the preimplantation period is vulnerable to perturbations. Review of these studies provides clinically useful information and a basis for investigations of the long-term effects of assisted reproduction technology on the children conceived.

Increasing twinning rates in Norway, 1967–2004: the influence of maternal age and assisted reproductive technology (ART)

The incidence of twin pregnancies is increasing in industrialized countries, including Norway. In the present nationwide study from Norway, we aimed at evaluating the effect of assisted reproductive technologies and delayed childbearing age on this epidemic rise. Altogether 2.19 million pregnancies, including 27,849 twin pairs and higher-order multiples, were included in this population-based study with data from the Medical Birth Registry of Norway covering the years 1967-2004. The study period was divided into two, 1967-87 and 1988-2004, respectively. For the last time period, pregnancies from assisted reproductive technologies were available through a separate registration, and these data were linked with the Medical Birth Registry of Norway birth record. Additionally, we compared the twinning rates from natural conception in the two time periods in relation to maternal age. Logistic regression was used for adjusted odds ratio estimation. During 1967-1987, the twinning rate remained constant at 1.0% of the total number of births in Norway. Thereafter, the total twinning rate increased from 1.1% in 1988 to 1.9% in 2004. After excluding pregnancies from assisted reproductive technologies, the increase was from 1.1% to 1.6% in this period. There was a significantly higher twinning rate in all age groups in the time period 1988-2004 compared with 1967-1987. In naturally conceived pregnancies, OR for twins were 1.11 (95% CI 1.05-1.17) in the age group 20-24 years, 1.25 (95% CI 1.19-1.31) in the age group 30-34, and 1.36 (95% CI 1.11-1.67) in the age group 40-44 comparing the two time periods. The multiple pregnancy rate increased by 50% in Norway during the time period 1988-2004, even when twin pregnancies from assisted reproduction were excluded. Maternal age and assisted reproductive technologies cannot alone satisfactorily explain the rise in the twinning rate in Norway.

Assisted reproductive technology has been detrimental to academic reproductive endocrinology and infertility: depth of the problem and possible solutions

Dr. Soules' editorial points out some, but not all, of the detrimental effects of assisted reproductive technology on the subspecialty of academic reproductive endocrinology and infertility. This response adds to the list of problems (i.e., discussing the loss of pure endocrinology) but points out an example of a creative solution (i.e., merging academic units with private practices).

Laboratorial Rules for Choosing the Elective Single Embryo to be Transferred: Morphological Parameters

The high incidence of multiple pregnancies is a major side effect of assisted reproductive technology that has recently given rise to justified criticism from different sides. The only efficacious measure to reduce the incidence of twin pregnancies is a policy of single-embryo transfer. The objective of this study was determined the main morphological non-invasive parameters able to select embryos with highest implantation potential to be transferred in an elective single embryo transfer (eSET) program.

Number of Transferred Embryos: How to Reduce Multiple Pregnancies

Because the diagnostic tools for predicting whether an early cleavage stage embryo can lead to a viable pregnancy are still elusive, transfer of more than one embryo remains quite common. However, the only way to reduce multiple pregnancies, considered as the main adverse effect of assisted reproductive technology, is to transfer a single embryo. In countries such as Switzerland and Germany, the law allows cryopreservation only at the 2-pronuclear stage. This restricts considerably the possibility of selecting the embryos to be transferred. Therefore, a good cryopreservation program at the 2-pronuclear stage is an essential tool to optimize the efficiency of in vitro fertilization (IVF). We therefore recommend the Cumulated Singleton Delivery Rate (CUSIDERA) as a measure of standard IVF efficiency. This rate averages approximately 23.5% when calculated over the last 10 years in our unit and reaches a value above 35% for patients with more than 10 zygotes. Elective single-embryo transfers and the decrease of iatrogenic multiple pregnancies in IVF remain dependent on better prognostic tools for the appropriate selection of patients, gametes, and zygotes.

Ovulation induction, assisted conception and childhood cancer

Rapid advances have been made in the treatment of infertility over the last 30 years following the introduction of in vitro fertilisation and intracytoplasmic sperm injection. Whilst effects of assisted reproductive technology (ART) on birth outcomes are well documented little is known about effects on child health after the neonatal period. Childhood cancer is one area warranting further examination. The hypothesis that cancer in children may be initiated during early fetal development means that events leading up to and around conception may be important. Whilst the few large-scale epidemiological studies that have looked at childhood cancer incidence following ART have failed to find any significant increased risk, some case-control studies have reported an increased risk of specific cancers. However, it is important not to over interpret these findings as the reason for the infertility may be the predisposing factor, rather than the procedure itself. Recent recommendations by the UK’s National Health Service to offer intra-uterine insemination and one free treatment cycle for infertile couples will result in increasing numbers of children born following ART. More detailed investigations that include larger numbers plus sufficient follow-up periods and information on the underlying causes of the infertility are needed since long term outcomes for these children, in particular the risk of developing cancer, remain largely unknown.

Recent decelerated decline in perinatal mortality rate of unlike-sexed twins in Japan.

The effect of assisted reproductive technology is more pronounced in unlike-sexed twins than in like-sexed. Trends in perinatal mortality of twins were compared between the two types of sex combination. Certificates for births (478,276 cases), stillbirths (50,542 cases), and early neonatal deaths (8747 cases) were the subjects of this analysis. Since 1984, the decline in the perinatal mortality of unlike-sexed twins has been slower than that of like-sexed twins. In both light-for-dates (LFD) and non-LFD, the decline in the gestational age standardised mortality ratio has been slower in unlike-sexed twins. We suggest this is due to the introduction of assisted reproductive technologies.

Risk of cancer in the offspring of women who underwent ovarian stimulation for IVF.

Over the past decade attention has been increasingly focused on the long-term health effects of assisted reproductive technologies (ART), such as IVF, in both women and their offspring. To determine the risk of cancer in children conceived by IVF we used a large population-based historical cohort that was initially designed to examine the risk of gynaecological disorders in women who underwent IVF. Children were included in the exposed group if they were conceived by IVF or other related fertility techniques (n=9484). The unexposed group consisted of 7532 children whose mothers were diagnosed with subfertility disorders but who were conceived naturally. All cohort members were asked to complete a mailed questionnaire that inquired about reproductive variables and cancer in the offspring (response rate 66.9%). During an average follow-up period of 6.0 years, 16 cancers were observed in the exposed and unexposed group combined, whereas 15.5 were expected [standardized incidence ratio (SIR) = 1.0; 95% confidence interval (95% CI) 0.6-1.7]. A direct comparison between children conceived after ART and naturally conceived children revealed no increased risk for childhood malignancies [risk ratio (RR) = 0.8; 95% CI 0.3-2.3]. Despite the small numbers of observed cancer cases, these findings demonstrate that children conceived by ART have no greatly increased risk of cancer during childhood compared with the general population and the internal reference group.

Single-embryo transfer.

The high incidence of multiple pregnancy is a major side effect of assisted reproductive technology that has recently given rise to justified criticism from different sides. The reasons for the high incidence of multiple pregnancies are discussed and a brief review is given of the steps that have been proposed to solve or at least reduce the problem. In this article, attention is particularly focused on the prevention of twin pregnancies because in terms of perinatal morbidity and associated costs, they outweigh the effect of high-order multiple pregnancies when expressed in absolute figures. The only efficacious measure to reduce the incidence of twin pregnancies is a policy of single-embryo transfer. We report on our experience with elective single-embryo transfer in good prognosis patients (age <37 years, first two in vitro fertilization (IVF) cycles and at least two embryos of high quality). About one-third of the couples meeting these criteria agreed to have a single embryo transferred, at least during their first IVF cycle. Pregnancy rates in women who had an elective single-embryo transfer (more than one high-quality embryo available) were only slightly lower than those in the group with elective double (i.e., more than two high-quality embryos available) transfer (37.9 vs. 40.0%) but the incidence of twins was 0.0 versus 27.1%. This strategy resulted in a substantial decrease of the twin pregnancy rate from 27.0 to 14.9%, without affecting the overall pregnancy rate. The conditions that are to be fulfilled before this policy can and will be applied on a large scale are discussed.

Medical, cognitive, emotional, and behavioral outcomes in school-age children conceived by In-Vitro Fertilization

Assessed long-term effects of assisted reproduction technologies of in-vitro fertilization (IVF) and related techniques of embryo transfer (ET) on children's adjustment. 51 school-age Israeli children conceived by IVF'ET were compared with 51 control- matched children conceived spontaneously. The assessment includeda comprehensive medical evaluation, a psychological examination, teachers' reports, parents' reports, and children's self-reports. As compared with controls, NF/ET children did not reveal significant differences in physical and neurological status or on cognitive measures of IQ, visual-motor coordination, visual memory, and verbal comprehension. Nevertheless, the IVFET children were scored lower by teachers on measures of socioemotional adjustment in school and on self-report measures of anxiety, aggression, and depression. Among NFET children, the tendency to be at a greater risk for emotional disturbances was exacerbated among boys and among children whose parents were older.

The effects of in vitro fertilization on subsequent pregnancy outcome

Objective: The purpose of this study was to look at the effects of assisted reproductive technology on subsequent pregnancy outcome variables. Methods: This retrospective study was performed using the Regional Perinatal Data System, a population-based birth registry. The data system is used by all 23 hospitals in the 14-county region of Central New York. 42,656 births were analyzed from January 1, 1995 through December 31, 1996. The associations between in vitro fertilization and premature rupture of membranes (PROM), preterm delivery (PTD), age, gravidity, parity, and race were evaluated using χ 2 and Fisher’s two-tailed Exact analyses. Odds ratios represent the magnitude of the association. Results: PROM PTD Nulli- parous ≥35 Years Old Race Primi- gravida Odds ratio 4.73 16.05 2.00 5.31 1.88 2.36 P value <.001 <.001 <.01 <.001 NS <.001 Women undergoing in vitro fertilization were significantly more likely to experience PTD and PROM. They were significantly more likely to be nulliparous, primigravidas, or over the age of 34. Conclusions: This analysis shows a strong association between women who have undergone in vitro fertilization and adverse pregnancy outcomes including PROM and preterm delivery. This study suggests a need for intensified obstetric care and the assignment of high risk pregnancy status to those women who have undergone in vitro fertilization. This association has not been previously reported and underscores the need for a comprehensive data system to analyze adverse events within a region and develop strategies for prevention.

10 The implantation window

The implantation window is defined as that period when the uterus is receptive for implantation of the free-lying blastocyst. This period of receptivity is short and results from the programmed sequence of the action of oestrogen and progesterone on the endometrium. Implantation itself is a process that commences with apposition, continues through attachment to trophoblast outgrowth and decidualization. For maximal effectiveness of assisted reproductive technologies in women, it is important to know the optimal time for embryo transfer which implies a need to predict the period of uterine receptivity. At present there are no good markers of, or for prediction of, uterine receptivity. In cycles where endogenous hormonal activity is suppressed or absent, the optimal time for embryo transfer can be easily defined and lies between luteal days +3 to +5, where luteal day +1 is the first day of exogenous progesterone treatment. In the human, it is suggested that blastocyst apposition begins about LH day +6 and is complete by LH +10. Human embryos survive in vitro manipulation well, and the stage of development at which they are placed in the uterus seems less critical than in other species, provided they are at an earlier stage of development than that of the endometrium.