Jacques Balayla

The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation

Absolute uterine factor infertility (UFI) refers to the refractory causes of female infertility stemming from the anatomical or physiological inability of a uterus to sustain gestation. Today, uterine factor infertility affects 3–5% of the population. Traditionally, although surrogacy and adoption have been the only viable options for females affected by this condition, the uterine transplant is currently under investigation as a potential medical alternative for women who desire to go through the experience of pregnancy. Although animal models have shown promising results, human transplantation cases have only been described in case reports and a successful transplant leading to gestation is yet to occur in humans. Notwithstanding the intricate medical and scientific complexities that a uterine transplant places on the medical minds of our time, ethical questions on this matter pose a similar, if not greater, challenge. In light of these facts, this article attempts to present the ethical issues in the context of experimentation and standard practice which surround this controversial and potentially paradigm‐altering procedure; and given these, introduces “The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation”, a set of proposed criteria required for a woman to be ethically considered a candidate for uterine transplantation.

Technical Update: Preimplantation Genetic Diagnosis and Screening

OBJECTIVE To update and review the techniques and indications of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). OPTIONS Discussion about the genetic and technical aspects of preimplantation reproductive techniques, particularly those using new cytogenetic technologies and embryo-stage biopsy. OUTCOMES Clinical outcomes of reproductive techniques following the use of PGD and PGS are included. This update does not discuss in detail the adverse outcomes that have been recorded in association with assisted reproductive technologies. EVIDENCE Published literature was retrieved through searches of The Cochrane Library and Medline in April 2014 using appropriate controlled vocabulary (aneuploidy, blastocyst/physiology, genetic diseases, preimplantation diagnosis/methods, fertilization in vitro) and key words (e.g., preimplantation genetic diagnosis, preimplantation genetic screening, comprehensive chromosome screening, aCGH, SNP microarray, qPCR, and embryo selection). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies published from 1990 to April 2014. There were no language restrictions. Searches were updated on a regular basis and incorporated in the update to January 2015. Additional publications were identified from the bibliographies of retrieved articles. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. (Table 1) BENEFITS, HARMS, AND COSTS: This update will educate readers about new preimplantation genetic concepts, directions, and technologies. The major harms and costs identified are those of assisted reproductive technologies. SUMMARY Preimplantation genetic diagnosis is an alternative to prenatal diagnosis for the detection of genetic disorders in couples at risk of transmitting a genetic condition to their offspring. Preimplantation genetic screening is being proposed to improve the effectiveness of in vitro fertilization by screening for embryonic aneuploidy. Though FISH-based PGS showed adverse effects on IVF success, emerging evidence from new studies using comprehensive chromosome screening technology appears promising. Recommendations 1. Before preimplantation genetic diagnosis is performed, genetic counselling must be provided by a certified genetic counsellor to ensure that patients fully understand the risk of having an affected child, the impact of the disease on an affected child, and the benefits and limitations of all available options for preimplantation and prenatal diagnosis. (III-A) 2. Couples should be informed that preimplantation genetic diagnosis can reduce the risk of conceiving a child with a genetic abnormality carried by one or both parents if that abnormality can be identified with tests performed on a single cell or on multiple trophectoderm cells. (II-2B) 3. Invasive prenatal or postnatal testing to confirm the results of preimplantation genetic diagnosis is encouraged because the methods used for preimplantation genetic diagnosis have technical limitations that include the possibility of a false result. (II-2B) 4. Trophectoderm biopsy has no measurable impact on embryo development, as opposed to blastomere biopsy. Therefore, whenever possible, trophectoderm biopsy should be the method of choice in embryo biopsy and should be performed by experienced hands. (I-B) 5. Preimplantation genetic diagnosis of single-gene disorders should ideally be performed with multiplex polymerase chain reaction coupled with trophectoderm biopsy whenever available. (II-2B) 6. The use of comprehensive chromosome screening technology coupled with trophectoderm biopsy in preimplantation genetic diagnosis in couples carrying chromosomal translocations is recommended because it is associated with favourable clinical outcomes. (II-2B) 7. Before preimplantation genetic screening is performed, thorough education and counselling must be provided by a certified genetic counsellor to ensure that patients fully understand the limitations of the technique, the risk of error, and the ongoing debate on whether preimplantation genetic screening is necessary to improve live birth rates with in vitro fertilization. (III-A) 8. Preimplantation genetic screening using fluorescence in situ hybridization technology on day-3 embryo biopsy is associated with decreased live birth rates and therefore should not be performed with in vitro fertilization. (I-E) 9. Preimplantation genetic screening using comprehensive chromosome screening technology on blastocyst biopsy, increases implantation rates and improves embryo selection in IVF cycles in patients with a good prognosis. (I-B).

Maternal Marital Status and the Risk of Stillbirth and Infant Death: A Population-Based Cohort Study on 40 Million Births in the United States

OBJECTIVE The objective of our study was to evaluate the association between maternal marital status and the risk of fetal and infant death, including sudden infant death syndrome (SIDS). METHODS We conducted a population-based cohort study using the Centers for Disease Control and Preventions Linked Birth-Infant Death and Fetal Death data on all births in the United States between 1995 and 2004. Marital status was obtained from the birth certificate. The adjusted effect of marital status on the risk of fetal and infant mortalities was estimated using unconditional logistic regression analysis. RESULTS The cohort consisted of 40,529,306 births, of which 37,461,715 met study criteria. There were 130,353 stillbirths (3.5/1,000 births) and 140,175 infant deaths (3.8/1,000 births), of which 24,066 were due to SIDS (0.6/1,000 births). Rates of nonmarital births increased from 31.3% to 35.4% over the study period. As compared with births from married women, births from unmarried women were at an increased risk of stillbirths (relative rise [RR], 1.24; 95% confidence interval [CI], 1.21-1.26), total infant deaths (RR, 1.45; 95% CI, 1.42-1.47), and SIDS (RR, 1.70; 95% CI, 1.63-1.78). Among unmarried women, those at a higher risk of fetal and infant death were women under 15 or over 40 years of age, African-American women, and those who received no prenatal care. CONCLUSION Nonmarital childbearing seems to be associated with an increased risk of fetal and infant death, including SIDS. Promoting access to care and targeting unmarried mothers-to-be with the goal of educating, increasing awareness, and providing resources for proper obstetrical and maternal care may be of great benefit to their pregnancies.

The Effect of Pelvic Size on Cesarean Delivery Rates: Using Adolescent Maternal Age as an Unbiased Proxy for Pelvic Size

OBJECTIVES Dystocia, the presence of abnormal labor, is the most common indication for cesarean delivery. Risk factors for dystocia include abnormalities of expulsatile forces during labor, fetal factors, and maternal pelvic size abnormalities. The objective of our study was to evaluate the effect of pelvic size on the risk of cesarean delivery rates using adolescent maternal age as an unbiased determinant of pelvic size. METHODS We conducted a population-based cohort study using the Center for Disease Control and Preventions Linked Birth-Infant Death and Fetal Death data on all births in the US between 1995 and 2004 for women aged 12 to 20. We excluded all births of gestational age under 24 weeks and those with reported congenital malformations or chromosomal abnormalities. Maternal age and mode of delivery information was obtained from the birth records. RESULTS There were 6,188,704 births in our cohort of which 1,863 were to women aged 12; 12,903 to women aged 13; 68,890 to women aged 14, and the remainder to women aged 15 and above. Cesarean delivery rates were highest amongst women aged 12 at 19.59 % and declined to 13.92% amongst 15 year-olds, and 14.84 % amongst 20 year olds. This effect was more pronounced when the analysis was restricted to macrosomic fetuses (P<0.005). CONCLUSION Cesarean delivery rates increase the younger the maternal age is suggesting that pelvic factors can play an important role in dystocia.

Impact of maternal obesity on the incidence of pregnancy complications in France and Canada

The aim of our study was to compare the impact of maternal obesity on the incidence of medical complications of pregnancy in France and Canada. We performed a prospective comparative cohort study using French data, retrieved from a prospective cohort of singleton deliveries, and Canadian data retrieved from QUARISMA, a cluster-randomized controlled trial conducted in Quebec, both between 2009 and 2011. Outcomes studied included, hypertensive disorders of pregnancy (HDP), venous thromboembolism, stillbirth, caesarean delivery and macrosomia. The impact of obesity across both cohorts was studied using univariate and multivariate logistic regression analyses, adjusting for relevant confounders. The French and Canadian databases included 26,973 and 22,046 deliveries respectively, with obesity rates of 9.1% and 16% respectively (p < 0.001). In both cohorts, obesity was significantly associated with an increased rate of HDP, cesarean delivery, and macrosomia. However, in both cohorts the relationship between increasing body mass index and the incidence of medical complication of pregnancy was the same, regardless the outcome studied. In conclusion, obesity is a risk factor for adverse maternal and fetal outcomes in both cohorts. Similar trends of increased risk were noted in both cohorts even though obesity is more prevalent in Canada.

Uterine transplantation is not a good use of limited resources: FOR: Uterine transplantation is not a good use of limited resources—a case of distributive justice and burden of disease

JACQUES BALAYLA, PHYSICIAN, CANADA, ELIAS M DAHDOUH, MEDICAL DIRECTOR, CANADA ....................................................................................................................................................................... The debate surrounding uterine transplantation (UTx) is complex and multifaceted. Although its scientific merit has recently been put in the spotlight, the social, economic and ethical considerations implicated have been largely left out of the mainstream conversation.