Fetal reduction for everyone?

Infertility treatments have benefited millions of couples to have their own children; however, the complication of multiple pregnancies with their increased morbidity and mortality has created significant problems. Fetal reduction (FR) was developed to ameliorate these issues. Over 30 years of publications show that FR has been highly successful in substantially reducing both mortality and morbidity. As with most radically new techniques, initial cases were in the "nothing to lose" category. With experience, indications liberalize, and quality of life issues increase as a proportion of cases. Overall risks for twins are not twice as those for singletons, but they are approximately 4- to 5-fold higher. In experienced hands, the combination of genetic testing by CVS followed by FR has made most multiples behave statistically as if they were originally the lower number. The use of microarray analysis to better determine fetal genetic health before deciding on which fetus(es) to keep or reduce further improves pediatric outcomes. With increasing experience and lower average starting numbers, the proportion of FRs to a singleton has increased considerably. Twins to a singleton FR now constitute an increasing proportion of cases performed. Data on such cases show improved outcomes, and we believe FR should be at least discussed and offered to all patients with a dichorionic twin pregnancy or higher. eSET is not a panacea because of the resultant monochorionic twins.

Fetal reduction and twins.

Infertility treatments have allowed millions of couples to have their own children, but resultant multiple pregnancies with their increased morbidity and mortality have been a significant complication. Fetal reduction was developed to ameliorate this issue. Over 30 years of publications show that fetal reduction has been highly successful in substantially reducing both mortality and morbidity related to multiple pregnancies. As with most radically new techniques, initial cases were in the "nothing to lose" category. With experience, indications liberalize, and quality of life issues gain relevance. The overall risks of twin pregnancy are not twice that of singleton pregnancy; they are about 4 to 5 times higher. In experienced hands, the combination of genetic testing by chorionic villus sampling followed by fetal reduction has made the outcomes of most multiple pregnancies statistically equivalent to those of pregnancies with lower fetal numbers. Use of microarray analysis to better determine fetal genetic health before deciding on which fetus(es) to keep or reduce further improves pediatric outcomes. With increasing experience and lower average starting numbers, the proportion of fetal reductions to a singleton has increased considerably. Twins to a singleton fetal reductions now constitute an increasing proportion of cases performed. Data on such cases show improved outcomes, and we believe fetal reduction should be at least discussed and offered to all patients with a dichorionic twin pregnancy or higher. With the increasing reliance on elective single-embryo transfers, monochorionic twins, which have much higher complication rates than dichorionic twins, have increased substantially. Furthermore, monochorionic twins cannot be readily and safely reduced, so the adverse perinatal statistics of elective single-embryo transfer are a major setback for good outcomes. Although elective single-embryo transfer is appropriate for some, we believe that for many couples, the transfer of 2 embryos is generally a more rational approach.

The epidemic of abnormal copy number variant cases missed because of reliance upon noninvasive prenatal screening.

OBJECTIVE: To assess the implications of increasing utilization of noninvasive prenatal screening (NIPS), which may reach 50% with the concomitant decrease in diagnostic procedures (DPs) for its impact on detection of chromosomal abnormalities. METHODS: We studied our program's statistics over 5 years for DPs and utilization of array comparative genomic hybridization (aCGH). We then modeled the implications in our program if DP had not fallen and nationally of a 50% DP and aCGH testing rate using well-vetted expectations for the diagnosis of abnormal copy number variants (CNVs). RESULTS: Our DP fell 40% from 2013-2017. Utilization of aCGH for DP nearly tripled. We detected 28 abnormal CNVs. If DP had not fallen, we likely would have detected 60. With 4 million US births per year, 2 million DPs would detect 30 000 abnormal CNVs and 4000 standard aneuploidies. At a 1/500 complication-pregnancy loss rate, the detection/complication ratio is 8.5/1. CONCLUSIONS: Noninvasive prenatal screening has significantly changed the practice of prenatal screening. However, while increasing the detection of Down syndrome, the concomitant decrease in DP and lack of aCGH results in missing many more abnormalities than the increase in Down syndrome and complications of DP combined. From a public health perspective, such represents a missed opportunity for overall health care delivery.

Sequential Amniotic Fluid Thyroid Hormone Changes Correlate with Goiter Shrinkage following in utero Thyroxine Therapy.

Several isolated reports of fetal goiter treatment have shown limited generalizability of approaches and provide no real guidance for optimal timing, dosages, and treatment strategies. Graves' disease accounts for >60% of these cases. Maternal treatments of hyperthyroidism include antithyroid medications such as methimazole and more commonly propylthiouracil (PTU). Here, our management of a patient with a fetal thyroid goiter from maternal exposure to PTU diagnosed at 23.6 weeks' gestation and the management of other cases allow us propose a general strategy for treatment. Intrauterine therapy with 200 and then 400 µg of levothyroxine (3 weeks apart) showed an 85% reduction in fetal thyroid goiter volume. We collected amniotic fluid samples at the time of treatments and assayed thyroid hormones and associated antibodies which closely reflected the changes in thyroid goiter mass volume. Our observations suggest a weekly or biweekly therapeutic intervention schedule. Utilizing both goiter size as well as a novel approach in using amniotic fluid hormone levels to monitor therapy efficacy might improve the quality of treatments. Only with a standardized approach and collection of amniotic fluid thyroid panels do we have the opportunity to develop the database required to determine the number and timing of treatments needed.

Paternity balancing.

BACKGROUND: Gestational carriers and egg donors have been used by 'traditional' and now increasingly, gay couples. Three gay male couples, all using egg donors and gestational carriers with semen from both partners, had triplets. All desired reductions to twins for the standard medical indications, but requested, if reasonably possible, to have twins with one fathered by each partner. METHODS: Following our usual clinical protocol, we performed chorionic villus sampling at 12 weeks on all fetuses obtaining FISH and karyotype. For paternity analysis, 14 polymorphic molecular markers on villi were compared to DNA samples from the two men to include or exclude each. RESULTS: Standard assessments were all normal. Paternity testing showed that one partner fathered two of the triplets, and the other one. In all cases, one of the 'twins' was reduced with good clinical outcomes ensuing. CONCLUSIONS: Paternity balancing increases options for satisfying family planning desires of gay male couples. We believe it comparable to gender preferences in reductions, i.e. it can be considered but only completely subservient to any clinical criteria. Paternity balancing raises similar ethical issues as reduction with gender preferences, but may increase patient autonomy and mainstream acceptance of stable, gay families.