Association of state insurance mandates for fertility treatment with multiple embryo transfer after preimplantation genetic testing for aneuploidy

IMPORTANCE: Multiple gestation is one of the biggest risks after in vitro fertilization (IVF), largely due to multiple embryo transfer (MET). Single embryo transfer (SET) uptake has increased over time and has been attributed to various factors, such as mandated insurance coverage for IVF and preimplantation genetic testing for aneuploidy (PGT-A). OBJECTIVE: To investigate whether mandates for IVF insurance coverage are associated with decreased use of MET after PGT-A. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using data on embryo transfers reported to the Society for Assisted Reproductive Technology between 2014 and 2016. Data were analyzed from January to October 2021. EXPOSURES: State-mandated coverage for fertility treatment and type of cycle transfer performed (PGT-A, untested fresh, and untested frozen). MAIN OUTCOMES AND MEASURES: Use of MET compared with SET, live birth, and live birth of multiples. RESULTS: There were 110 843 embryo transfers (mean [SD] patient age, 34.0 [4.5] years; 5520 individuals identified as African American [5.0%], 10 035 as Asian [9.0%], 5425 as Hispanic [4.9%], 45 561 as White [41.1%], and 44 302 as other or unknown race or ethnicity [40.0%]); 17 650 transfers used embryos that underwent PGT-A. Overall, among transferred embryos that had PGT-A, there were 9712 live births (55.0%). The odds of live birth were 70% higher with MET vs SET after frozen embryo transfer with PGT-A (OR, 1.70; 95% CI, 1.61-1.78), but the risk of multiples was 5 times higher (OR, 5.33; 95% CI, 5.22-5.44). The odds of MET in cycles with PGT-A in states with insurance mandates were 24% lower than in states without mandates (OR, 0.76; 95% CI, 0.68-0.85). CONCLUSIONS AND RELEVANCE: This study found that despite the promise of using SET with PGT-A, MET after PGT-A was not uncommon. This practice was more common in states without insurance mandates and was associated with a high risk of multiples

Adenomyosis presenting as a molar pregnancy: A case report

•We present a case of atypical adenomyosis with clinical, laboratory, and imaging findings suggestive of a molar pregnancy.•Adenomyosis causes uterine enlargement and may appear cystic on vaginal ultrasound.•Falsely elevated β-hCG in the setting of obesity and hypothyroidism may complicate diagnosing abnormal uterine bleeding

Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.

The importance of bone morphogenetic protein 2 (BMP2) in the skeleton is well known. BMP2 is expressed in a variety of tissues during development, growth and healing. In this study we sought to better identify the role of tissue-specific BMP2 during post-natal growth and to determine if BMP2 knockout affects the ability of terminally differentiated cells to create high quality bone material. We targeted BMP2 knockout to two differentiated cell types known to express BMP2 during growth and healing, early-stage osteoblasts and their progeny (osterix promoted Cre) and vascular endothelial cells (vascular-endothelial-cadherin promoted Cre). Our objectives were to assess post-natal bone growth, structure and strength. We hypothesized that removal of BMP2 from osteogenic and vascular cells (separately) would result in smaller skeletons with inferior bone material properties. At 12 and 24 weeks of age the osteoblast knockout of BMP2 reduced body weight by 20%, but the vascular knockout had no effect. Analysis of bone in the tibia revealed reductions in cortical and cancellous bone size and volume in the osteoblast knockout, but not in the vascular endothelial knockout. Furthermore, forelimb strength testing revealed a 30% reduction in ultimate force at both 12 and 24 weeks in the osteoblast knockout of BMP2, but no change in the vascular endothelial knockout. Moreover, mechanical strength testing of femurs from osteoblast knockout mice demonstrated an increased Young's modulus (greater than 35%) but decreased post-yield displacement (greater than 50%) at both 12 and 24 weeks of age. In summary, the osteoblast knockout of BMP2 reduced bone size and altered mechanical properties at the whole-bone and material levels. Osteoblast-derived BMP2 has an important role in post-natal skeletal growth, structure and strength, while vascular endothelial-derived BMP2 does not

Whole body DXA results at 12 and 24 weeks for WT and cKO male mice.

<p>(A) Body weight was significantly reduced in the Osx-Cre cKO and unchanged for VEC-Cre mice. (B) Percent fat was not significantly reduced in the 12- and 24week old Osx-Cre cKO male mice (although it did reach significance at 24 weeks when male and female data were pooled (ANOVA)). (C) Osx-Cre cKO male mice showed a significant reduction in BMC at the 12-week time point, with a non-significant trend at 24 weeks (which was significant when male and female data were pooled (ANOVA)). BMC was unchanged for VEC-Cre mice at either time point.</p

Deletion of BMP2 was evaluated in osteogenic cells (Osx-Cre) and vascular cells (VEC-Cre).

<p>(A) First, Cre activation was verified by examination of cortical bone (ulna) and muscle from transverse cross-sections through the mid-forelimb. In control samples the bone is completely black. The Osx-Cre mouse has a GFP::Cre fusion protein which demonstrated the current expression of Cre in some osteocytes within the bone and osteoblasts lining the bone surface (open white arrowheads). The VEC-Cre mouse was crossed with mTmG reporter mouse and demonstrated Cre activation within muscle and periosteum compartments surrounding the bone (filled white arrowheads). (B) Confirmation of the BMP2 protein deletion was done using immunohistochemistry. In the control sample BMP2 expression was seen in the muscle (blue filled arrows) and bone-lining cells (thin black arrows). Using the Osx-Cre BMP2 expression was absent in the bone lining cells, but abundantly expressed throughout the muscle compartment (blue filled arrows). In contrast, using the VEC-Cre expression of BMP2 was limited to osteoblasts lining the bone surface (thin black arrows). Images are representative of 3–5 sections from 3–6 animals/group.</p

MicroCT was used to assess structural properties of the tibia at 12/16 and 24 weeks.

<p>(Osx-Cre data shown at 12 weeks, VEC-Cre data shown at 16 weeks.) Osx-Cre cKO mice had (A) shorter tibia and (B) reduced cortical bone volume with no change in (C) cancellous BV/TV or (D) cortical TMD. VEC-Cre mice showed no differences in any parameter. (E) Illustrations of cortical bone geometry show a smaller marrow cavity in the Osx-Cre cKO mice.</p

In vivo microCT results from tibia midshaft and metaphyseal regions.

z<p>p<0.05 BMP2 fl/fl; VEC-Cre+ vs. BMP2 fl/fl; VEC-Cre−.</p>a<p>p<0.05 BMP2 fl/fl; Osx-Cre+ vs. BMP2 fl/fl; Osx-Cre−.</p