Recent advances in reproductive technology.
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Humans↗
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The development and impact of culture media for assisted reproductive technologies.
Changes in the composition of media used for human in vitro fertilization and embryo culture are reviewed, and their impact on improved pregnancy rates is discussed. It is concluded that changes to the formulation of culture media for assisted reproductive technologies over the past decade have played a significant role in improving outcomes from assisted reproductive technologies procedures involving the culture of embryos.
Blastocyst↗
Obesity and assisted reproductive technology outcomes.
Obesity is a rising health problem in Western societies. It has been related to increased morbidity and mortality rates due to several pathologies. In the field of gynaecology and reproduction, obesity is associated with menstrual disorders, hirsutism, infertility, miscarriage and obstetric complications. It is known to impair human reproduction through different mechanisms such as insulin resistance, hyperandrogenism and elevated leptin levels. Weight management and dietary intervention can reverse this situation and improve reproductive function. Obesity can also impair the outcome of assisted reproductive technologies. The lower probability of a healthy live birth described in obese women seems to be the result of a combination of lower implantation and pregnancy rates, higher preclinical and clinical miscarriage rates and increased complications during pregnancy for both mother and fetus. Studies performed in infertile women undergoing assisted reproduction technologies indicate that the ovary plays a leading, but not exclusive, role in the fertility prognosis of these patients. The endocrine and metabolic environment may affect oocyte quality and, therefore, embryo development, implantation and pregnancy outcome. The endometrium seems to play a subtle role in the more negative reproductive outcome of obese women, according to recent studies based on the ovum donation model.
Endometrium↗
Assisted reproductive technology. A clinical appraisal.
With the various types of reproductive technology now available, the overall pregnancy rates still are less than 25%. An increase in those rates would permit physicians to provide relief from infertility to a much larger population.
Embryo Transfer↗
Day 3 serum inhibin-B is predictive of assisted reproductive technologies outcome.
OBJECTIVE: To determine if women with day 3 serum inhibin-B concentrations < 45 pg/mL (conversion factor to SI unit, 1.00) demonstrate a poorer response to ovulation induction and assisted reproductive technologies outcome relative to women with inhibin-B values > or = 45 pg/mL. DESIGN: Analysis of inhibin-B, FSH, and E2 concentrations in day 3 serum samples. SETTING: Academic clinical practice. PATIENT(S): One hundred fifty-six women who underwent 178 assisted reproductive technology (ART) cycles with luteal phase GnRH agonist suppression plus hMG and urofollitropin stimulation. MAIN OUTCOME MEASURE(S): Serum E2 on day of hCG, number of oocytes retrieved per patient, fertilization rate, cleavage rate, clinical pregnancy rate (PR) per initiated cycle, cancellation rate per initiated cycle, and spontaneous abortion rate. RESULT(S): Women with day 3 serum inhibin-B < 45 pg/mL demonstrated 70% of the E2 response, had 66.6% of the number of oocytes retrieved per patient, with 28% of the clinical PR per initiated cycle, and three times the cancellation rate per initiated cycle than women with day 3 inhibin-B > or = 45 pg/mL. After controlling for age, day 3 serum FSH, day 3 serum E2, patient cycle number, and method of ART, day 3 serum inhibin-B > or = 45 pg/mL was noted to be prognostic of the number of oocytes retrieved and clinical PR. The adjusted odds ratio of clinical pregnancy for those with day 3 serum inhibin-B > or = 45 pg/mL versus those with inhibin-B < 45 pg/mL was 6.8 (95% confidence interval 1.8 to 25.6). CONCLUSION(S): Women with low day 3 serum inhibin-B concentrations demonstrate a poorer response to ovulation induction and are less likely to conceive a clinical pregnancy through ART relative to women with high day 3 inhibin-B.
Adult↗
No country is an island: comment on the House of Commons report Human Reproductive Technologies and the Law.
In its recent report Human Reproductive Technologies and the Law, the House of Commons' Select Committee on Science and Technology insisted that the United Kingdom 'does not take a purely insular view' on sex selection but to carefully consider the impact on other countries before allowing changes to current legislation. True, no country is an island, not even the British Isles. Still, outlawing a harmless practice in Great Britain because of its alleged harmful effects in other countries is bad public policy.
China↗
Analysis of 104 twin pregnancies conceived with assisted reproductive technologies and 193 spontaneously conceived twin pregnancies.
OBJECTIVE: To evaluate pregnancy outcome of assisted reproductive technology (ART)-conceived twin pregnancies. DESIGN: Retrospective study. SETTING: A tertiary obstetric care center. PATIENT(S): All twin pregnancies delivered > or = 24 weeks of gestation from January 1, 1996, to December 31, 1997. INTERVENTION(S): Maternal and neonatal record review. MAIN OUTCOME MEASURE(S): Pregnancy and perinatal outcome. RESULT(S): The study group comprised 104 ART-conceived twin pregnancies, and 193 non-ART-conceived pregnancies served as controls. Mean maternal age, the proportion of nulliparae, and the percentage of women who delivered before 34 weeks' gestation was higher among the study women, whereas mean gestational age was younger. The incidences of pregnancy-induced hypertension, uterine bleeding, premature contractions, intrauterine growth retardation, fetal death, discordance, and cesarean section were significantly higher in the study group. Correspondingly, in the study group, the mean birth weight of both twins was lower; more neonates weighed < 1, 500 g, more had Apgar scores of < 7 at 5 minutes, more were admitted to the intensive care unit, and more second twin neonates died. The outcome of twin pregnancies conceived spontaneously was comparable with those conceived by ovulation induction. CONCLUSION(S): Assisted reproductive technology-conceived twin pregnancies are at greater risk than non-ART-conceived ones for pregnancy complications and adverse perinatal outcome.
Female↗
Preconception care and treatment with assisted reproductive technologies.
Couples with fertility problems seeking treatment with assisted reproductive technologies (ART) such as in vitro fertilization should receive preconception counseling on all factors that are provided when counseling patients without fertility problems. Additional counseling should address success rates and possible risks from ART therapies. Success rates from ART are improving, with the highest live birth rates averaging about 40% per cycle among women less than 35 years old. A woman's age lowers the chance of achieving a live birth, as do smoking, obesity, and infertility diagnoses such as hydrosalpinx, uterine leiomyoma, or male factor infertility. Singletons conceived with ART may have lower birth weights. Animal studies suggest that genetic imprinting disorders may be induced by certain embryo culture conditions. The major risk from ovarian stimulation is multiple gestation. About one-third of live-birth deliveries from ART have more than one infant, and twins represent 85% of these multiple-birth children. There are more complications in multiple gestation pregnancies, infants are more likely to be born preterm and with other health problems, and families caring for multiples experience more stress. Transferring fewer embryos per cycle reduces the multiple birth rate from ART, but the patient may have to pay for additional cycles of ART because of a lower likelihood of pregnancy.
Age Factors↗
Attitudes of Israeli gynecologists regarding candidate screening and personal responsibility in assisted reproductive technologies versus adoption in Israel.
BACKGROUND: Although both assisted reproduction technologies (ART) and adoption services are designed to help childless couples, their legal status is overwhelmingly different. In particular, applicants for adoption services in Israel are required to undergo a meticulous background check, whereas ART has no such precondition. The present study evaluated the attitude of gynecologists in Israel towards this difference and their opinion of their own responsibility to children born by in vitro fertilization (IVF) treatment. METHODS: One hundred and eighty-one gynecologists were asked to complete a questionnaire covering their opinions on the acceptance of applicants for IVF programs compared to adopting couples and their professional responsibility to children born by IVF. RESULTS: Average age of the responders was 47.9+/-9.2 years; 75% were male; average number of own children was 2.6+/-1.3. Sixty-one percent believed that the use of IVF conferred a duty upon the physician to ensure the well-being of the future child, and 66% believed it important to somehow screen potential parents. Forty percent favored equalizing the preconditions for IVF candidates and adopting couples. Thirty-five percent supported changing the adoption laws to make the process easier, and 33% supported changing the IVF program to prevent unsuitable candidates from starting therapy. Among the latter, a strong marital bond was considered important by 17%, health status of the potential parents by 72%, and possession of a criminal record by 35%. Forty percent favored parental evaluation by a social worker, and 66%, by a psychological assessment. Only 24% thought that economic status was important. CONCLUSIONS: Most gynecologists in ART programs believe they have a duty to look out for the unborn child. Approximately one-third support the institution of changes in parental evaluation to facilitate the adoption process and to provide more restrictions in ART programs. Most believed that parental evaluation, preferably by a psychological assessment, is important prior to starting an IVF program.
Adoption↗
Assisted reproductive technologies: professional and legal restrictions in Australian clinics.
The professional and legal regulation of assisted reproductive technologies (ART) in Australia is a vast maze of intersecting laws and guidelines which place restrictions on the provision of services such as infertility treatment, surrogacy, sex selection for social reasons, donor insemination, pre-implantation diagnosis and human embryo research. This study investigated the application of these restrictions on clinical practice in New South Wales, a relatively unregulated State, and Victoria, a relatively highly regulated State. The results of the survey indicate that the range of ART services in Victorian clinics was far more limited than in New South Wales clinics. The Victorian clinics uniformly restricted access of single and lesbian women and did not offer social sex selection procedures. The New South Wales clinics adopted different polices regarding these services. It was found that restrictive laws governing "social" issues have a significant impact on the availability of ART services and some respondents seemed unclear about the nature of restrictions and laws relevant to their work. It was also found that "reproductive tourism" is prevalent and restrictions were circumnavigated by patients with assistance from clinics. It was concluded that more evidence is required to evaluate regulation in this field of medicine.
Ambulatory Care Facilities↗
Serum progesterone in predicting pregnancy outcome after assisted reproductive technology.
PURPOSE: Our purpose was to determine whether serum progesterone predicts pregnancy outcome after superovulation. METHODS: One hundred twenty-three consecutively pregnant patients were divided into three groups: group I, 55 patients following superovulation for assisted reproductive technologies; group II, 23 patients after correction of oligoovulation; and group III, 45 patients who conceived spontaneously. When beta-human chorionic gonadotropin was positive, progesterone was measured on the same serum sample. A serum progesterone level of 45 microns/L was set to differentiate between nonviable pregnancy and ongoing pregnancy. RESULTS: In group I, zero (0%) of 38 ongoing pregnancies and 10 (59%) of 17 nonviable pregnancies were observed with a progesterone level of < 45 microns/L [14.2 ng/ml (P < 0.001)]. In group II, 4 (27%) of 15 ongoing pregnancies and 5 (63%) of 8 nonviable pregnancies had a progesterone level of < 45 microns/L (P = NS). In group III, 10 (42%) of 24 ongoing pregnancies and 15 (71%) of 21 nonviable pregnancies were observed with a progesterone level of < 45 microns/L (14.2 ng/ml) (P = NS). CONCLUSIONS: A serum progesterone level of < 45 nM predicts nonviable pregnancy after superovulation for assisted reproductive technology.
Chorionic Gonadotropin↗
Adoption, infertility, and the new reproductive technologies: problems and prospects for social work and welfare policy.
In this article, the author examines the social and psychological issues raised by infertility and addresses problems resulting from the increasing commercialization of children through adoption practices as well as through the proliferation of new reproductive technologies. The author begins with a discussion of infertility and considers some aspects of adoption, the traditional solution to infertility. Some historical, technical, ethical, psychological, and social aspects of artificial insemination, along with newer developments of surrogacy, such as in vitro fertilization and frozen embryos, also are discussed. Recommendations are suggested for meeting the service needs of people who have problems associated with infertility. Finally, the author stresses the importance of research along with the necessity for social workers to take a leadership role in helping society both to understand the ethical issues related to and to develop enlightened public policy on infertility, adoption, and the new reproductive technologies.
Adoption↗
[Assisted reproductive technologies reported in the National Registry of Israel 1995-1996].
National registration of the results of assisted reproductive technology (ART) is maintained by many countries. The Israel Committee for Registry of ART asked 19 in-vitro fertilization (IVF) units in 1995 and 20 in 1996 to report on their activities and results. Data were collected by questionnaires and analyzed by computer. The most common ovarian stimulation was the combination of GnRH agonist and gonadotropins. There were 10.89 treatment cycles in 1995, of which 45% were with intracytoplasmic sperm injection (ICSI). In 1996, of 12.72 cycles, 54% were with the ICSI procedure. Embryos were transferred into the uterine cavity in 90% of the conventional IVF cycles and in 95% of the ICSI cycles. The overall pregnancy rate was 22% per embryo transfer in the conventional IVF and ICSI cycles. The delivery rate was 13.7% and 15.4% per embryo transfer in the conventional IVF and ICSI cycles, respectively. The rates for abortion and tubal pregnancy were 24% and 1.3%, respectively. These results are better than in previous years and are comparable with results in some western European countries. Efforts are being made to convert the registry into a real-time computerized system.
Female↗
[The risk of congenital malformations and genomic imprinting defects in assisted reproductive technologies and nuclear transfer cloning].
Recent studies show that assisted reproductive technologies (ART), whether in vitro fertilization (IVF) or intra-cytoplasmatic sperm injection (ICSI) or applied to cloning by somatic cell nuclear transfer (SCNT) are associated to a higher risk of congenital malformations and errors in deprogramming, maintenance or reprogramming genomic imprinting in humans and animals. IVF and ICSI are also associated to an increased admission to neonatal intensive care units and more need for health care resources in infancy. A mutagenic effect of a chemical used in SCNT has been reported and gene depression was found in bovine embryos obtained by IVF or SCNT. The causes of these anomalies could be pathological conditions for which ART is applied, a direct effect of technologies on the zygotes or embryos, avoidance for zygotes or embryos of the oviduct path that is needed to elicit necessary immunity or genomic programming processes, or adaptive selective steps acquired during thousands of millions of generations in evolution. The knowledge of evolution is emphasized as essential in the scientific ethical analysis.
Animals↗
Legal and ethical aspects of new reproductive technologies; the case of prenatal diagnosis.
The introduction of new reproductive technologies raises numerous legal and ethical questions. Answering these questions requires conceptual clarity about the nature and scope of women's and parental rights, the implications of these techniques for the dignity and rights of the unborn and the responsibility of the state as well as the medical profession in preserving the proper use of these techniques. One of the technologies that requires scrupulous consideration is the technique of prenatal diagnosis. In this essay an effort is made to explore the meaning of the main rights and interests at stake, to assess the (potential) benefits and hazards of prenatal diagnosis for both women/couples and unborn children, and to identify some criteria that could serve as a yardstick to measure the permissible use of this technique.
Ethics, Medical↗
Are children born after assisted reproductive technology at increased risk for adverse health outcomes?
As assisted reproductive technologies (ARTs) are increasingly used to overcome infertility, there is concern about the health of the children conceived. The empirical evidence for associations with outcomes related to child health is variable and should be evaluated with consideration of methodological shortcomings. Currently, there is convincing evidence that ART treatment may increase the risk of a few outcomes. Experimental laboratory studies document that various constituents in culture media affect various embryo characteristics both positively and negatively. Multiple-gestation pregnancy and birth are increased with ART, both because of multiple embryo transfer and embryo splitting. There is evidence of an increase in chromosomal abnormalities among pregnancies conceived using intracytoplasmic sperm injection and low birth weight and preterm delivery among singletons conceived with all types of ART; however, there remains uncertainty about whether these risks stem from the treatment or the parental infertility. For some outcomes, data of an increased risk with ART are suggestive at best largely because of lack of purposeful study of sufficient size and scope. These include specific perinatal morbidities, birth defects, developmental disabilities, and retinoblastoma. The evidence for an association between ART and spontaneous abortion is inconsistent and weak. There is inconclusive evidence that ART may be associated with genetic imprinting disorders. For childhood cancer, chronic conditions, learning and behavioral disorders, and reproductive effects there is insufficient empirical research to date, but given the data for more proximal outcomes, these outcomes merit further study. Future research needs to address the unique methodological challenges underlying study in this area.
Abortion, Spontaneous↗
Implementation of assisted reproductive technologies following conservative management of FIGO grade I endometrial adenocarcinoma and/or complex hyperplasia with atypia.
OBJECTIVE: The objective was to report a series of infertility therapy outcomes following conservative management of endometrial adenocarcinoma and/or complex hyperplasia with atypia. METHODS: A retrospective review of the University of Iowa assisted reproductive technology database was performed. All women presenting with International Federation of Obstetrics and Gynecology (FIGO) grade I uterine adenocarcinoma and/or complex hyperplasia with atypia were assessed for type and duration of medical management, initial, interim treatment, and preinfertility treatment endometrial biopsy (BX) findings. Assessment of infertility treatment outcomes and postinfertility endometrial biopsy findings were performed. All of the pathology samples were re-reviewed at the Gynecologic Oncology Tumor Board to confirm the diagnosis by a pathologist with a particular expertise in gynecologic pathology. RESULTS: Four infertile women, three nulligravid and one primigravid, were evaluated with the diagnosis of FIGO grade 1 endometrial adenocarcinoma and/or complex hyperplasia with atypia desiring to preserve fertility. Two women with FIGO grade 1 endometrial adenocarcinoma were successfully treated with high-dose progestational agents resulting in normal proliferative endometrium. In addition, both women with complex hyperplasia with atypia were successfully treated with progestins and/or ovulation induction. Successful pregnancy outcomes were achieved for three of the four women with assisted reproductive technology. A total of five successful pregnancies and eight healthy live-born infants were achieved among three women. One of the four women was unable to conceive despite three cycles of in vitro fertilization. Hysterectomy was performed for recurrent complex hyperplasia with atypia. In our series, we found it can take 3-10 months (mean, 6.25 months; median, 6 months) to obtain benign endometrium preceding infertility therapy. CONCLUSION: This report demonstrates that conservative management of well-differentiated endometrial adenocarcinoma and/or complex hyperplasia with atypia followed by aggressive assisted reproduction is an option to highly motivated and carefully selected women.
Adenocarcinoma↗
Imprinting and assisted reproductive technology.
In the past 25 years, the frequency of assisted reproductive technology (ART) births has increased rapidly to account for 1-2% of all births in many developed countries. ART procedures such as in vitro fertilization and intracytoplasmic sperm injection are generally considered to be safe, but recent studies suggest a small excess of birth defects and low-birth weight in ART children. In addition, several clinical studies have reported an increased frequency of ART conceptions among children with Beckwith-Wiedemann syndrome or Angelman syndrome caused by an imprinting defect. Although these studies require further confirmation, they are consistent with animal studies reporting disordered expression and epigenetic changes in imprinted genes following in vitro embryo culture. The absolute risk of an imprinting disorder after ART appears to be very small, but further data are required to determine whether the association between ART and human imprinting disorders reflects the effect of embryo culture (or some other aspect of ART) and/or a common mechanism for infertility and imprinting disorders. Retinoblastoma and neurodevelopmental defects have been only tentatively linked to ART, but in view of the role of epigenetic processes in the regulation of gene expression in development and cancer, further research is required into long-term health outcomes for ART children and the epigenetic consequences of ART protocols.
Angelman Syndrome↗