UK approves three-parent fertility treatments and more research

Three-parent fertility treatment approved by UK Parliament

FDA committee considering similar action

A form of assisted reproductive technology that could make it possible for women with mutations in mitochondrial DNA to give birth to children free of mitochondrial disease has been approved by UK’s House of Commons. A Food and Drug Administration (FDA) committee is considering granting similar approval for use of the technique-known as oocyte modification or three-parent gene therapy-in the United States.

Reporting in The New England Journal of Medicine, investigators from Newcastle University, Newcastle upon Tyne, estimated that approximately 150 births annually could be impacted if clinics in the United Kingdom were licensed to perform the procedure. The technique involves injection of cellular material from a healthy donor egg into an unfertilized egg from a woman with mitochondrial disease prior to in vitro fertilization (IVF). When the ooplasm is transferred during IVF, it thus contains genetic material from three individuals: the biological parents and the ooplasm donor.  

More: The ob/gyn generalist and fertility evaluation and treatment

Mitochondria are membrane-enclosed cytoplasmic organelles responsible for synthesis of ATP by oxidative phosphorylation for use in energy-requiring processes in the cell. Accumulations of mitochondrial mutations throughout a person’s life may contribute to the aging process, cancer, and a number of metabolic diseases.

The UK action, which must be approved by the House of Lords, was controversial because the alterations in an embryo’s DNA can be passed on to subsequent generations. Among the risks being considered by the FDA Cellular, Tissue, and Gene Therapies Advisory Committee are epigenetic changes that could put a fetus at risk of diseases or developmental problems related to aberrant imprinting, alteration in the number of mitochondria, and carryover of mutant mitochondria. 

Next: How valuable is cfDNA testing for Trisomy 21?

Meta-analysis underscores value of cell-free DNA screening for Down syndrome

A meta-analysis by Nicolaides and colleagues confirms that use of cell-free (cf) DNA is superior to all other traditional methods of screening for trisomy 21. However, expanding indications for the testing to trisomies 18 and 13 and sex chromosome aneuploidies would increase the cumulative false-positive rate (FPR) by eight-fold.

The findings, published in Ultrasound in Obstetrics & Gynecology, are based on data from 37 peer-reviewed studies of cfDNA testing for aneuploidies published between January 2011 and January 4, 2015. Summary statistics with 95% confidence intervals (CIs) were derived for each study and then combined to arrive at pooled summary statistics, using fixed-effects and random-effects models.

Editorial: Dr. Lockwood on the promise of cfDNA screening for aneuploidies

All of the studies reported on cfDNA results in relation to the fetal karyotype from invasive testing or clinical outcome. The weighted pooled detection rates (DRs) and FPRs) in singleton pregnancies were 99.2% (95% CI, 98.5–99.6%) and 0.09% (95% CI, 0.05–0.14%) for trisomy 21;  96.3% (95% CI, 94.3–97.9%) and 0.13% (95% CI, 0.07–0.20) for trisomy 18; and 91.0% (95% CI, 85.0–95.6%) and 0.13% (95% CI, 0.05–0.26%) for trisomy 13.   In singleton pregnancies, the DR and FPR for monosomy X were 90.3% (95% CI, 85.7–94.2%) and 0.23% (95% CI, 0.14–0.34%) and 93.0% (95% CI, 85.8–97.8%) and 0.14% (95% CI, 0.06–0.24%) for sex chromosome aneuploidies other than monosomy X. In twin pregnancies, the FPR for trisomy 21 was 0.23% (95% CI, 0.00–0.92%) and the DR was 93.7% (95% CI, 83.6–99.2%).

Because cfDNA testing can be carried out at the 10^th or 11^th week of gestation, the authors noted, it has the advantage of providing reassurance to many parents that their fetus is unlikely to be trisomic and, for the minority with affected fetuses, the option of earlier, safer termination. They recommend implementing cfDNA testing contingent on results of first-line screening with a different test, preferably the first-trimester combined test. That strategy, they said, would lead to a very high DR and a lower cost than were cfDNA testing used for first-line screening.

NEXT: Why are adolescents using the withdrawal method?

The realities of withdrawal method use in young adults

According to a recent analysis of national survey data, young adults who use the withdrawal method were more likely to view pregnancy positively and to believe that condoms would diminish sexual pleasure. The findings suggest a need to incorporate a discussion about attitudes toward pregnancy and pleasure when counseling this population about contraception.

Using data from the 2006 to 2010 National Survey of Family Growth, researchers from the University of Wisconsin – Madison found that 14% of young women and 17% of young men reported any use of withdrawal at last sex. The report reflected information on 3597 sexually active women and men aged 15 to 24 years who were at risk of an unintended pregnancy. Associations with the withdrawal method were documented through logistic regression.

More: Teens educated about LARCs use them when cost isn't an issue

Among the population, 7% of young women and 6% of young men reported only using the withdrawal method the last time they’d engaged in sex. Several sociodemographic factors were associated with use of withdrawal, but the strongest linkage was to attitudes about pregnancy and condoms. Young women who indicated that they would be pleased about an unintended pregnancy were 2.2 to 2.6 times as likely to have used any/only withdrawal (P <.01) as those who said they would not be pleased with such a pregnancy. Both males and females who felt that condoms would diminish pleasure were more likely to have used any/only withdrawal at the last sexual encounter (odds ratio=1.8–2.6, P<.05).

The investigators concluded that a greater number of young adults were using the withdrawal method in conjunction with other methods of contraception than only using that method alone. This finding indicates that doctors may wish to speak about the use of the withdrawal method, distinguishing between only using it and using it with other methods. The investigators also urged doctors to assess and discuss pregnancy expectations and attitudes about pleasure when providing counseling about contraception.