Role Of Assisted Reproductive Technologies Research Articles

Deformational plagiocephaly at birth: an observational study on the role of assisted reproductive technologies

ABSTRACTBackground: Following the “back to sleep” recommendations, a striking rise in deformational plagiocephaly (DP) occurred. However, additional maternal, pregnancy and infant conditions may play a role.Objectives: We aimed to evaluate the prevalence of and risk factors for DP at birth. Additionally, given the association between assisted reproductive technologies (ART) use and unfavorable pregnancy events, we explored the association between ART and DP.Patients and Methods: A total of 413 neonates >33 weeks born at L. Sacco Hospital (Milan, Italy) from May 2011 through to January 2012 were enrolled. Data regarding parental, conceivement, pregnancy and delivery characteristics were recorded. Infants’ skull measurements, including the oblique cranial length ratio (OCLR) were taken within 72 h after birth. Plagiocephaly was defined for OCLR > 105.9.Results: The prevalence of DP was 20.3%. It was associated with twinning (OR 5.0; 95%CI 2.22–11.1), pregnancy complications (OR 2.86; 95%CI 1.49–5.26), prematurity (OR 2.13; 95%CI 0.98–4.54), ART use (OR 2.00; 95%CI 0.90–4.35) and male gender (OR 1.79; 95%CI 0.94–2.50). Adjusting for multiple pregnancies however, the association between ART and DP disappeared.Conclusion: Results show that offspring of pregnancies conceived through ART do not have increased risk of DP. However, our numbers are small thus larger studies are needed for definitive conclusions.

Intracytoplasmic morphologically selected sperm injection (IMSI) after repeated IVF or ICSI failures: a prospective comparative study

Sperm morphology plays a significant role in assisted reproductive technologies and is associated with high implantation rates. The objective of this study was to evaluate the outcome of intracytoplasmic morphologically selected sperm injection (IMSI) after repeated failures of conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) techniques. In a prospective study in which couples acted as their own controls, 75 infertile couples were offered IMSI after at least two previous IVF or ICSI failures. The main outcome measures were embryo quality and number of blastocysts obtained. The percentage of top quality embryos obtained at day 2 was increased in IMSI compared to IVF/ICSI cycles (89.8% versus 79.8%; p=0.009). Extended embryo culture was possible in 41.3% of IMSI cycles versus 26.7% of IVF/ICSI cycles (p=0.04), and the mean number of blastocysts obtained was higher in IMSI cycles (1.5±1.9) than in IVF/ICSI cycles (1.0±1.2) (p=0.03). Moreover, IMSI resulted in clinical pregnancy and birth rates of respectively 29.3% and 18.6%. After two or three IVF/ICSI failures, IMSI seems to give better embryo quality and more blastocysts, which allow more embryo transfers at the blastocyst stage. This study supports the use of sperm ultramorphology examination as an independent test to be proposed after repeated IVF or ICSI failures.

Cerebral Palsy and Assisted Conception

Assisted reproductive technologies have been widely used over the past 30 years, and 1% to 4% of births worldwide are products of these technologies. However, adverse health outcomes related to assisted reproductive technologies, including cerebral palsy, have been reported. We extracted and reviewed all relevant studies cited by Medline from 1996 to 2010 evaluating the role of assisted reproductive technologies as a causative factor for cerebral palsy and poor long-term neurologic outcome. The research suggests that multiple pregnancy, preterm delivery, and babies small for gestational age are factors in the development of cerebral palsy. The vanishing embryo syndrome may also play a role. We review the evidence for these potentially causative factors, as well as their implications for embryo transfer policies.

Extracts from a traditional Chinese herbal remedy (Zhuyun recipe) improve endometrial receptivity in mice with embryonic implantation dysfunction and ovulation stimulation

Although ovarian stimulation has an important role in assisted reproductive technologies (ART), it may also have detrimental effects on endometrial receptivity. Traditional Chinese herbal remedy, as a kind of traditional treatments, has been widely and increasingly applied in clinic. In this article, the impact of traditional Chinese medicines (TCM) on embryonic implantation, pregnant rate and underlying mechanisms will be investigated. One hundred and sixty-three female pregnant kunming mice were randomly divided into 6 groups, including A, control group; B, ovulation stimulation (OS) group; C, OS+TCM group; D, embryo implantation dysfunction (EID) group; E, EID+TCM group; F, TCM only group. Uterus samples were collected at gestation Day 4 and were detected with immunohistochemistry and Real Time-PCR analyses. Uterine horns were excised to determine the number of pregnant mice and implantation sites on the Day 8 postcoitum. OS group and EID group showed a significant decrease in pregnant rate and the expression of both the endometrial leukaemia inhibitory factor (LIF) and integrin β3 subunit during the implantation window. OS+TCM group and EID+TCM group showed a higher pregnant rate and endometrial LIF and integrin β3 subunit expression compared to OS group and EID group. The number of implanted embryo in EID group was lower than in control group, but higher in EID+TCM group than in EID group. No significant difference was found in the measured indices between the TCM only group and control group. OS model and EID model may have a negative influence on endometrial receptivity and embryonic implantation in mice. Conversely, TCM appears to reverse the expression of endometrial LIF and integrin β3 subunit, improves the uterine receptivity in mice and increases pregnant rate and embryonic implantation. It provides a new insight into the clinic infertility's treatment.

Ovarian Hyperstimulation Syndrome Prevention Strategies: In Vitro Maturation

The only reliable way to eliminate the risk of ovarian hyperstimulation syndrome (OHSS) is complete avoidance of gonadotropin ovarian stimulation. It could be argued that in vitro maturation (IVM) of oocytes represents the most effective strategy to prevent OHSS. IVM has been an established treatment option in many centers worldwide for over a decade. The use of IVM and natural cycle in vitro fertilization (IVF) combined with IVM can result in clinical pregnancy rates that compare to those obtained with conventional IVF. The obstetric and perinatal outcomes of IVM pregnancies are similar to those conceived from stimulated IVF or spontaneous conceptions. To date, more than a thousand healthy infants have been born without an increase in fetal abnormalities. Although IVM may not replace standard IVF, it plays an increasingly important role in assisted reproductive technology, especially in the settings of high responders and those patients at risk of OHSS.

The role of assisted reproductive technology in the management of recurrent pregnancy loss

Description of genetic screening of preimplantation embryos as a means of reducing miscarriages in patients with recurrent pregnancy loss. That the promise of preimplantation genetic screening (PGS) for ameliorating recurrent pregnancy loss has been fulfilled is controversial. An array of comparative studies has suggested a positive effect of PGS on implantation rate, but these have been balanced by studies showing no effect or a negative effect, highlighting the need for more rigorously designed studies and randomized controlled trials. Emerging technologies may provide more information from the embryo biopsies even as the mosaicism of the embryo and its implications for interpreting PGS data are recognized. Through the screening of embryos for abnormality in chromosome number or structure and selecting only normal embryos for transfer, PGS was envisioned and applied as a therapeutic tool for improving implantation and live birth rates from in-vitro fertilization and providing a means of attenuating pregnancy loss in recurrent pregnancy loss patients. An array of reports on the effects of PGS on embryo implantation and live birth rates has been made since its introduction, showing, variously, increases, decreases or no changes in these parameters. Various factors may influence the efficacy of PGS, including the patient population to which it is applied, technical aspects such as embryo biopsy, the genetic analysis and embryo culture environment, the current limitation of the genetic analysis (a subset of, rather than all, the 24 chromosomes) and the mosaicism of the embryo and blastocyst. Collectively, these contribute to the challenge of optimizing PGS and understanding how the screening result reflects the ultimate genetic constitution of the conceptus. Emerging cytogenetic and molecular technologies such as comparative genomic hybridization and microarray analysis may provide a broader appraisal of the embryo for a more comprehensive evaluation of developmental potential and prognosis for live birth.

HLA-G molecules in pregnancy and their possible role in assisted reproductive technology

Pregnancy is commonly considered a semi-allograft, as half of the fetal genome derives from the father. However, in normal pregnancy, several tolerance mechanisms have been demonstrated to counteract the maternal immune response. Among these, the expression of HLA-G by invasive cytotrophoblasts has shown to play a role in creating a tolerogenic condition at the feto–maternal interface. The possible role of HLA-G molecules in pregnancy and as a marker for oocyte/embryo selection in assisted reproduction technology is reviewed in this article, and the contrasting results present in the literature is compared.

Infertility-related reproductive health knowledge and help-seeking behaviour in African countries

Data from African countries indicate that men and women attribute infertility to traditional beliefs about health and disease as well as to biomedical causes, although appropriate knowledge of the latter is frequently lacking. Infertility is a dreaded condition and as a result help-seeking is often intense and persistent. Most of the help-seeking is undertaken by women and both traditional and modern biomedical health services are accessed. There are, however, many barriers to effective and affordable biomedical infertility care, many of which are related to poor resources and lack of infrastructure, and as a result the need for infertility treatment is often unmet. Advances in the quality of care require greater commitment to the problem of infertility in African countries, the provision of health education as an integral part of infertility management, the integration of infertility services into reproductive health care programmes and defining the role of assisted reproductive technologies in low resource settings. At the same time the importance of traditional health services in infertility management should be recognized.

Treatment of infertility in women with pituitary tumors

Due to the pituitary’s critical position, a pituitary tumor may disrupt gonadal function, either by its expanding size or the inappropriate secretion of hormones. Menstrual cycles may be disrupted even without frank hypogonadism, particularly in the case of hormone-secreting adenomas. Despite optimal medical and surgical management of pituitary tumors, ovulation-induction therapy with gonadotropins is often required to restore fertility in these women. This article will provide an overview of the therapeutic options available for women with infertility resulting from pituitary tumors. Treatment strategies including dopamine agonists, gonadotropins and the role of assisted reproductive technologies will be discussed. Unique pregnancy considerations in the female patient with hypopituitarism will also be addressed.

P-523: Coculture with granulose cells of human oocytes during in vitro maturation and the influence on the maturation of ooplasm

IVM technique plays an important role in assisted reproductive technologies, especially for PCOS patients. The current in vitro culture medium can achieve nuclear maturation of oocytes rather than cytoplasmic maturation. This study is designed:firstly, to identify whether nuclear and cytoplasmic maturation can reach simultaneously in vitro maturation. Secondly, to observe if in vitro culture time can affect nuclear and cytoplasmic maturity of oocytes . Thirdly, Many animal experiments have identified that cocultured with monolayer granulose cells(GCs) can greatly improve the ooplasmic maturation, which is manifested in high fertilization rate, high embryo quality and high pregnancy rate. Our objectives were to confirm that cocultured with GCs can surely improve ooplasmic maturation of human oocytes. In this experiment, we used the linear distribution of cortical granules(CG) as the marker of cytoplasmic maturity of oocytes, since many reports have defined that. Prospective cohort study. Immature oocytes were retrieved from PCOS patients who were undergoing treatment from March to June 2005 at the Reproductive Medical Center in the Provincial Hospital of Shandong,all of whom had signed informed consents explicitly for this study. Pick-up of immature oocytes were performed 36 hours after HCG injection in natural menstruation cycles. Granulosa cells for coculture were taken from the cumulus-oocyte complexes (COC) in classical ICSI cycles. The COCs were digested with 80IU/ml hyaluronidase no more than 30 seconds. Then GCs were suspended with M-199 medium, centrifuged twice, 1000rpm for 10 mins. Then the suspension of granulose cells were dropped into 4-well plates and half of the culture medium was changed after 24 h. At that time, monolayer of GCs was formed and prepared for coculture with immature oocytes. Randomly,some of immature oocytes were cocultured with GCs and others were not cocultured in M-199 medium as control. All of them were evaluated 24h and 48h after in vitro maturation. The oocytes reached MII stage were labeled with FITC-LCA and observed under laser-scanning confocal microscope to investigate the distribution of CG. In comparison with the oocytes cultured in M-199 medium without granulose cells, the percentage of nuclear maturity after 24h, 48h in vitro maturation of cocultured oocytes were not significantly different respectively(36/69 vs 37/71,P>0.05;43/69 vs 43/71,P>0.05).The nuclear maturation rate of oocytes cultured for 48h are significantly higher than that of 24h in both control and experimental group (37/71 vs 43/71,P<0.05;39/69 vs 43/69,P<0.05).As for CG distribution pattern, the rate of peripheral distribution pattern is significantly higher in cocultured oocytes compared with control, either after cultured for 24h (27/39 vs 10/37,P<0.01) or cultured for 48h(31/43 vs 11/43,P<0.05),but for the comparison of maturality after in vitro maturation for 24hs between for 48hs in either control group or in co-culture group,no significant difference(10/37vs11/43,P>0.05;27/39vs31/43,P>0.05). It surely occurs that nuclear maturation and cytoplasmic maturation can not reach simutaneously during in vitro maturation. Cocultured with granulose cells monolayer can prompt greatly the cytoplasmic maturation of oocytes.Prolonged culture time can increase nuclear maturate rate but seem no helpful in cytoplasmic maturation.

Contemporary Obstetrics and Gynaecology for Developing Countries

Contemporary Obstetrics and Gynaecology for Developing Countries

Aromatase inhibitors in ovulation induction.

The new third generation aromatase inhibitors are extremely potent and specific oral inhibitors of estrogen production. We reported the success of using aromatase inhibitors for induction of ovulation in World Health Organization (WHO) type II anovulatory patients. Promising pregnancy rates were associated with the use of aromatase inhibitors for induction of ovulation in these women. In addition, the use of aromatase inhibition in conjunction with gonadotropin injection was associated with a significant reduction in the gonadotropin dose required for optimum controlled ovarian hyperstimulation. We believe that these oral agents are efficient and safe and have many advantages compared with clomiphene citrate (CC). We propose that aromatase inhibitors will replace CC in the future as the new primary treatment for ovulation induction. In this review, we present an update on the use of aromatase inhibitors for induction of ovulation and we discuss several new areas of potential interest regarding the use of aromatase inhibitors, either alone or together with recombinant follicle-stimulating hormone (FSH) for infertility treatment. Further research in these areas may demonstrate an expanded role in assisted reproductive technologies.

Research Update: Preterm Birth: A Continuing Challenge

Although preterm birth has been a major focus of study for the past two decades by health care providers in several disciplines, it remains more prevalent in the United States than in many developed countries and continues to be a prime reason for infant death (mortality) and illness (morbidity). In the past 10 years, preterm rates have risen in the United States from 10.6% in 1990 to 11.6% in 2000. Low birthweight rates have increased from 7.0% in 1990 to 7.6% in 2000. This column reviews recent studies addressing preterm and low birthweight births, including changing demographics, the role of assisted reproductive technology, smoking, domestic violence, the experience of women, and treatment strategies.

Preeclampsia in multiple gestation: the role of assisted reproductive technologies.

To estimate the relationship of assisted reproductive technologies and ovulation-inducing drugs with preeclampsia in multiple gestations. This historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously. Between January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty-nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at the P <.05 level. Women who conceive multiple gestations through assisted reproductive technologies have a 2.1-fold higher risk of preeclampsia than those who conceive spontaneously.

Preterm birth: a continuing challenge.

Although preterm birth has been a major focus of study for the past two decades by health care providers in several disciplines, it remains more prevalent in the United States than in many developed countries and continues to be a prime reason for infant death (mortality) and illness (morbidity). In the past 10 years, preterm rates have risen in the United States from 10.6% in 1990 to 11.6% in 2000. Low birthweight rates have increased from 7.0% in 1990 to 7.6% in 2000. This column reviews recent studies addressing preterm and low birthweight births, including changing demographics, the role of assisted reproductive technology, smoking, domestic violence, the experience of women, and treatment strategies.

Book Review: Iatrogenic Multiple Pregnancy: Clinical Implications

Individuals may pay large sums of money for assisted conceptions but it is usually the State that picks up the extra bill for neonatal care. In Iatrogenic Multiple Pregnancy, an attractive book full of personality, Blickstein and Keith offer a bold reminder that pregnancy at any cost is not necessarily in the best interests of couples, their children or society. We liked the way they allowed their contributors to express clear opinions. Although the needs of women undergoing assisted conception are sensitively acknowledged, a recurrent theme throughout the book is the risk associated with multiple pregnancy. In the USA the rate of multiple pregnancy has risen, though the role of assisted reproductive technologies in this is uncertain. The authors call for wider reporting, particularly of oral ovulation agent induced pregnancies. They particularly advocate limitation of higher-order multiple gestations, to improve outcome, and they stress that these difficult pregnancies should be managed in large units with specialist experience. Clearly, care should be transferred at the time of the diagnosis, not when the woman is in labour. The chapters on recognition of multiple pregnancies, planning of the pregnancy, diagnosis of abnormality, fetal reduction and multiple pregnancy delivery are all useful. Much stress is rightly put on early diagnosis of the pregnancy number, by careful uterine mapping and determination of chorionicity by ultrasound. Screening for fetal abnormality is also best undertaken early. We felt that the nuchal translucency issues were rather superficially described (e.g. without description of the different calculations by chorionicity). Especially important chapters are those on counselling parents and the implications for families of having high-order pregnancies—sometimes serious even if all the infants are born in good medical condition. There is a good account of the views of various religious faiths on assisted reproduction and the ethical considerations facing parents and health professionals involved in the care of these pregnancies. Finally, the legal implications of iatrogenic higher-order pregnancies are reviewed. The book is unusually illustrated with striking, nonscientific, black and white photographs (mostly of twins) which adorn each chapter and the cover. These are surprising, attractive and even at times distracting; on balance we felt they did not add to the book although they do remind the reader of the wonder of reproduction. The price is not so high that one resents this artistic addition. Another unusual feature is the inclusion of numerous ‘inserts’, including case histories, controversial discussions (such as cloning) and diagnostic pitfalls. This structure can break the reading flow, especially when a substantial proportion of a chapter is in these separate boxes. Sometimes the inserts give the impression they are updates, with references more recent than those in the body of the text. At other times the inserts seem to reflect difficulties with the structure of the book. For example, at the end there are eight ‘left-over’ sections on controversial points such as prolonged delayed delivery between multiples and discordant growth, grouped together. We felt that these sections would have been better integrated into the main text. Those with a particular interest in this area will wish to read Iatrogenic Multiple Pregnancy from cover to cover. It will also be a valuable occasional reference for any specialist involved in reproductive, fetal or maternal medicine as well as for neonatologists and some midwives.

Controlled micromanipulation of human sperm in three dimensions with an infrared laser optical trap: effect on sperm velocity

Individual human sperm can be micromanipulated in three dimensions using a 1.06 microns Nd:YAG laser trap. Single sperm swimming with velocities in the range of 65 to 85 microns/sec can be trapped with 40 mW of power through 120 seconds without a deleterious effect on velocity. Even though it will be necessary to further evaluate the effects of laser light on specific functions of sperm, our data suggest that decreasing the time of manipulation to a minimum will increase the safety of the micromanipulation procedures. Laser traps may play a role in assisted reproductive technology by facilitating the selective transport of individual sperm.