Minimal access to male fertility prices online: an analysis of the Society for Assisted Reproductive Technology (SART) clinics.

BACKGROUND: Though insurance coverage is evolving for male infertility services, most patients continue to pay out of pocket. These costs such as semen analysis and intracytoplasmic sperm injection preparation may affect the utilization of those services. We sought to determine online price transparency specifically for male infertility services on the websites of in-vitro fertilization (IVF) clinics in the US. METHODS: In this cross-sectional analysis, pricing data was acquired from each clinic on the Society for Assisted Reproductive Technology (SART) website as of July 2019. Each website was examined for availability and cost of services. Pricing data that required applying for a quote or a phone call was excluded. Mean price was calculated for each service. Additionally, practice location in an insurance coverage mandated state (ICMS) was also analyzed to evaluate for any effect on price transparency. RESULTS: Only 24.7% (89/361) of SART clinic websites included any pricing information. Of clinics with websites (361/383), 16.3% (59/361) had ≥2 prices reported and only 5.0% (18/361) had ≥6 prices reported. Only 3.6% (13/361) reported prices for male-related infertility services. Average semen analysis price was $161 of 10 reporting clinics. Four clinics reported sperm cryopreservation or annual sperm storage price, $388 and $555, respectively. Sperm retrieval cost $244 at the two reporting clinics. ICMS did not affect male price transparency, ICMS 3.1% (6/194) vs. non-ICMS 4.2% (7/167) (P=0.576). CONCLUSIONS: Price transparency of SART clinics on websites is relatively poor with only about one-quarter of clinics providing any cost information at all. Male infertility related pricing information is even more rarely reported compared to other IVF services potentially causing a stronger barrier for males to pursue infertility treatment.

Use of human-derived stem cells to create a novel, in vitro model designed to explore FMR1 CGG repeat instability amongst female premutation carriers.

OBJECTIVE: Create a model, using reprogrammed cells, to provide a platform to identify the mechanisms of CGG repeat instability amongst female fragile X mental retardation 1 gene (FMR1) premutation (PM) carriers. METHODS: Female PM carriers (with and without POI) and healthy controls were enrolled from June 2013 to April 2014. Patient-derived fibroblasts (FB) were reprogrammed to induced pluripotent stem cells (iPSC) using viral vectors, encoding KLF4, OCT4, SOX2, and MYC. FMR1 CGG repeat-primed PCR was used to assess the triplet repeat structure of the FMR1 gene. FMR1 promoter methylation (%) was determined using FMR1 methylation PCR (mPCR). Quantification of FMR1 transcripts by RT-qPCR was used to evaluate the effect of reprogramming on gene transcription, as well as to correlate patient phenotype with FMR1 expression. Production of FMR1 protein (FMRP) was determined using a liquid bead array-based immunoassay. RESULTS: Upon induction to pluripotency, all control clones exhibited maintenance of progenitor cell CGG repeat number, whereas 10 of 12 clones derived from PM carriers maintained their input CGG repeat number, one of which expanded and one contracted. As compared to parent FB, iPSC clones exhibited a skewed methylation pattern; however, downstream transcription and translation appeared unaffected. Further, the PM carriers, regardless of phenotype, exhibited similar FMR1 transcription and translation to the controls. CONCLUSIONS: This is the first study to establish a stem cell model aimed to understand FMR1 CGG repeat instability amongst female PM carriers. Our preliminary data indicate that CGG repeat number, transcription, and translation are conserved upon induction to pluripotency.

Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with "normal" CGG repeat status.

PURPOSE: The objective of this analysis is to examine the relationship between Fragile X Mental Retardation 1 gene (FMR1) cytosine-guanine-guanine (CGG) repeat number and ovarian reserve, with a particular focus exclusively on the range of CGG repeat number below the premutation (PM) range (<55 CGG repeats). METHODS: Our study included female patients who underwent assessment of FMR1 CGG repeat number and serum anti-Mullerian hormone (AMH) in 2009-2014. To examine the association between FMR1 repeat number and serum AMH, we created three summary measures of CGG repeat number for the two alleles-"Sum," "Max," and "Gap" (absolute difference). Using multivariable regression models, controlling for age, we then analyzed the impact of these summary measures on AMH. RESULTS: A total of 566 patients were included in our study. Using multivariable regression models, we found that the relationship between CGG repeat number and AMH differed depending on age. Specifically, in younger women, AMH increased by 7-8 % (Sum p < 0.01, Max p = 0.04) for every 1 unit increase in CGG repeat number. In contrast, starting at age 40, there was a 3 to 5 % decline in AMH for every 1 unit increase in CGG repeat number (Sum p < 0.01, Max p = 0.04). CONCLUSIONS: This is the first study to report a statistically significant correlation of ovarian reserve and CGG repeat number in women with <55 CGG repeats. Although these women are generally considered to have a normal phenotype, our data suggest that increasing CGG repeat number within this normal range is associated with a more rapid decline in ovarian reserve.

Reliability of 46,XX results on miscarriage specimens: a review of 1,222 first-trimester miscarriage specimens.

OBJECTIVE: To examine the rate of maternal contamination in miscarriage specimens. DESIGN: Retrospective review of 1,222 miscarriage specimens submitted for chromosome testing with detection of maternal cell contamination (MCC). SETTING: Referral centers requesting genetic testing of miscarriage specimens at a single reference laboratory. PATIENT(S): Women with pregnancy loss who desire complete chromosome analysis of the pregnancy tissue. INTERVENTION(S): Analysis of miscarriage specimens using single-nucleotide polymorphism (SNP) microarray technology with bioinformatics program to detect maternal cell contamination. MAIN OUTCOME MEASURE(S): Chromosome content of miscarriages and incidence of 46,XX results due to MCC. RESULT(S): Of the 1,222 samples analyzed, 592 had numeric chromosomal abnormalities, and 630 were normal 46,XX or 46,XY (456 and 187, respectively). In 269 of the 46,XX specimens, MCC with no embryonic component was found. With the exclusion of maternal 46,XX results, the chromosomal abnormality rate increased from 48% to 62%, and the ratio for XX to XY results dropped from 2.6 to 1.0. CONCLUSION(S): Over half of the normal 46,XX results in miscarriage specimens were due to MCC. The use of SNPs in MCC testing allows for precise identification of chromosomal abnormalities in miscarriage as well as MCC, improving the accuracy of products of conception testing.

Pregnancy During Recovery from Hematopoietic Stem Cell Transplant for Mycosis Fungoides.

We report a case of spontaneous pregnancy with subsequent full-term live birth following hematopoietic stem cell transplantation (HSCT) for mycosis fungoides in a 24-year-old nulligravida with 4 years of prior infertility due to primary ovarian insufficiency. Four months post-transplant, the patient was found to be 10 weeks pregnant. Her pregnancy was complicated by first trimester fetal exposure to mycophenolate mofetil (pregnancy category D), delayed-onset acute gastrointestinal graft-versus-host disease, and multiple systemic infections. This report highlights the importance of discussing potential fertility outcomes in patients undergoing HSCT, including the necessity for adequate contraception post-transplant, even in the setting of previous infertility.

Early pregnancy testosterone after ovarian stimulation and pregnancy outcome.

OBJECTIVE: To examine early pregnancy (EP) testosterone (T) after ovarian stimulation and its effect on singleton pregnancy outcomes. DESIGN: Prospective cohort study. SETTING: University-based tertiary care center. PATIENT(S): Subfertile women who conceived with or without fertility treatment. INTERVENTION(S): Ovarian stimulation for assisted reproduction, collection of serum total T levels in early pregnancy, and pregnancy follow-up. MAIN OUTCOME MEASURE(S): Rate of preterm delivery, low birth weight (LBW) (<2,500 g), and hypertensive disorders of pregnancy. RESULT(S): EP serum samples were measured from 266 singleton pregnancies. The mean T level among spontaneous conceptions was 74.90 ng/dL (SD 48.35 ng/dL); 103 ng/mL was the 90th percentile. Mean EP T was increased among patients who underwent ovarian stimulation compared with nonstimulated control subjects. In patients undergoing IVF, T levels in EP were linearly correlated with the number of oocytes retrieved. When pregnancy outcomes in women with normal T were compared with women with elevated T (>90th percentile), we did not see an increased risk for preterm delivery, hypertensive disorders of pregnancy, LBW infants, or cesarean delivery (odds ratio ratios 1.43, 0.38, 1.39, and 0.85, respectively). CONCLUSION(S): Elevations in EP T are associated with ovarian stimulation but do not appear to be associated with adverse pregnancy outcome. Further investigation to determine the etiology of increased maternal and neonatal morbidity among subfertile women is warranted.