Evaluation of at-home serum anti-Müllerian hormone testing: a head-to-head comparison study.

BACKGROUND: For optimal fertility testing, serum anti-Müllerian hormone levels are used in combination with other testing to provide reliable ovarian reserve evaluations. The use of the ADx 100 card is widely commercially available for at-home reproductive hormone testing, but data demonstrating that its results are reproducible outside of a clinical setting are limited, as well as comparisons of its performance with other newer blood collection techniques. This study aimed to evaluate the concordance of serum AMH levels found via standard venipuncture and self-administered blood collection using the TAP II device (TAP) and ADx card in women of reproductive age. METHODS: This was a prospective, head-to-head-to-head within-person crossover comparison trial that included 41 women of reproductive age (20-39 years). It was hypothesized that the TAP device would be superior to the ADx card both in terms of agreement with venipuncture reference standard and patient experience. Each subject had their blood drawn using the three modalities (TAP, ADx, and venipuncture). We evaluated the concordance of AMH assays from samples obtained via the TAP device and ADx card with the gold standard being venipuncture. Two-sided 95% CIs were generated for each method to compare relative performance across all three modes. Patient preference for the TAP device versus the ADx card was based on self-reported pain and Net Promoter Score (NPS). RESULTS: The TAP device was superior to the ADx card on all outcome measures. TAP R-squared with venipuncture was 0.99 (95% CI 0.99, > 0.99), significantly higher than the ADx card, which had an R-squared of 0.87 (95% CI 0.80, 0.94) under most favorable treatment. TAP sensitivity and specificity were both 100% (no clinical disagreement with venipuncture), versus 100 and 88%, respectively, for the ADx card. Average pain reported by users of the TAP device was significantly lower than the ADx card (0.75 versus 2.73, p < 0.01) and the NPS was significantly higher than the ADx card (+ 72 versus - 48, p < 0.01). CONCLUSIONS: The TAP was non-inferior to venipuncture and superior to the ADx card with respect to correlation and false positives. Moreover, the TAP was superior to both alternatives on patient experience. TRIAL REGISTRATION: NCT04784325 (Mar 5, 2021).

MicroRNA 21a-5p overexpression impacts mediators of extracellular matrix formation in uterine leiomyoma.

BACKGROUND: MicroRNAs (MiR) may promote fibroid development via altered expression of genes involved in cell proliferation and ECM formation, and evidence supports aberrant expression of MicroRNA (MiR) 21a-5p in fibroids. The purpose of this study was to investigate the functional significance of MiR 21a-5p overexpression in the pathobiology of leiomyomata (fibroids). METHODS: A basic science experimental design using immortalized fibroid and myometrial cell lines derived from patient-matched specimens was used. Stable overexpression of MiR-21a-5p in an immortalized fibroid and patient matched myometrial cell line was achieved through lentiviral vector infection. Main outcome measures were MiR-21-5p overexpression, target gene and protein expression, collagen (COL1A1) production, cell proliferation, cell migration, and cell cycle stages of fibroid and myometrial immortalized cell lines. RESULTS: MiR-21a-5p was overexpressed to similar levels in fibroid and myometrial cell lines after lentiviral infection. Increased expression of miR-21 resulted in increased gene and protein expression of TGF-ß3 in both fibroid and myometrial cells. Changes in expression of the ECM genes Fibronectin, Collagen 1A1, CTGF, Versican and DPT were seen in both fibroid and myometrial cells. Changes were also seen in Matrix Metalloproteinase (MMP) related genes including MMP 2, MMP 9, MMP 11 and Serpine 1 in both fibroid and myometrial cells. MiR-21 upregulation resulted in increased proliferation and migration in fibroid cells compared to myometrial cells. CONCLUSIONS: MiR-21a-5p overexpression results in changes in the expression of ECM mediators in both fibroid and myometrial cells, and increased cell proliferation in fibroid cells. These finding suggest a potential functional role of MiR-21a-5p in the development of uterine fibroids and warrant further investigation.

Clinical Characteristics Associated with Antibiotic Treatment Failure for Tuboovarian Abscesses.

OBJECTIVE: Although parenteral antibiotic treatment is a standard approach for tuboovarian abscesses, a significant proportion of patients fail therapy and require interventional radiology (IR) guided drainage. The objective of this study is to assess if specific clinical factors are associated with antibiotic treatment failure. STUDY DESIGN: Retrospective medical record review of patients hospitalized for tuboovarian abscesses from 2001 through 2012 was performed. Clinical characteristics were compared for patients who underwent successful parenteral antibiotic treatment, failed antibiotic treatment necessitating subsequent IR drainage, initial drainage with concurrent antibiotics, and surgery. RESULTS: One hundred thirteen patients admitted for inpatient treatment were identified. Sixty-one (54%) patients were treated with antibiotics alone. Within this group, 24.6% failed antibiotic treatment and required drainage. Mean white blood cell count (K/µL) (18.7 ± 5.94 versus 13.9 ± 5.12) (p = 0.003), mean maximum diameter of tuboovarian abscess (cm) (6.8 ± 2.9 versus 5.2 ± 2.0) (p = 0.03), and length of stay (days) (9.47 ± 7.43 versus 4.59 ± 2.4) (p = 0.002) were significantly greater for patients who failed antibiotic treatment. CONCLUSIONS: Admission white blood cell count greater than 16 K/µL and abscess size greater than 5.18 cm are associated with antibiotic treatment failure. These factors may provide guidance for initial selection of IR guided drainage.

Donor TSH level is associated with clinical pregnancy among oocyte donation cycles.

PURPOSE: The purpose of the study is to evaluate the association between donor TSH level (independent of recipient TSH level) and recipient pregnancy outcome among fresh donor oocyte IVF cycles. METHODS: This is a retrospective cohort study investigating 232 consecutive fresh donor-recipient cycles (200 total oocyte donors) at an academic medical center. Main outcome measures include clinical pregnancy and live birth. RESULTS: Cycles were categorized into two groups based on donor TSH level (< 2.5 and ≥ 2.5 mIU/L). After controlling for multiple donor and recipient characteristics, the probability of clinical pregnancy was significantly lower among donors with TSH levels ≥2.5 mIU/L compared to those with TSH values <2.5 mIU/L (43.1 %, 95 % CI 28.5-58.9, versus 66.7 %, 95 % CI 58.6-73.9, respectively, p = 0.01). The difference in live birth rates between the two groups did not achieve statistical significance (43.1 %, 95 % CI 28.8-58.6, versus 58.0 %, 95 % CI 50.0-65.6, respectively, p = 0.09). CONCLUSIONS: Donor TSH level, independent of recipient TSH level, is associated with recipient clinical pregnancy. These findings suggest that thyroid function may impact the likelihood of pregnancy at the level of the oocyte.

Ovarian stimulation and in-vitro fertilization outcomes of cancer patients undergoing fertility preservation compared to age matched controls: a 17-year experience.

PURPOSE: To compare the in-vitro fertilization (IVF) outcomes of cancer patients who underwent oocyte retrieval and embryo/oocyte cryopreservation prior to gonadotoxic therapy to those of age and time-matched controls with tubal factor infertility. METHODS: All cancer patients who underwent embryo/oocyte cryopreservation at our institution from 1997 to 2014 were reviewed. Primary outcomes were total dose of gonadotropins used, number of oocytes retrieved, and number of 2pn embryos obtained. Outcomes were compared to age-matched controls with tubal-factor infertility who underwent a fresh embryo transfer within the same relative time period as the IVF cycle of the cancer patient. RESULTS: Sixty-three cancer patients underwent 65 IVF cycles, and 21 returned for frozen embryo transfer. One hundred twenty-two age-matched controls underwent IVF cycles with fresh transfer, and 23 returned for frozen embryo transfer. No difference was seen between cancer patients and controls with respect to total ampules of gonadotropin used (38.0 vs. 35.6 respectively; p = 0.28), number of oocytes retrieved (12.4 vs. 10.9 respectively; p = 0.36) and number of 2pn embryos obtained (6.6 vs. 7.1 respectively; p = 0.11). Cumulative pregnancy rate per transfer for cancer patients compared to controls was 37 vs. 43 % respectively (p = 0.49) and cumulative live birth rate per transfer was 30 vs. 32 % respectively (p = 0.85). Cancer patients had a higher likelihood of live birth resulting in twins (44 vs. 14 %; p = 0.035). CONCLUSIONS: Most IVF outcomes appear comparable for cancer patients and age-matched controls. Higher twin pregnancy rates in cancer patients may reflect lack of underlying infertility or need for cancer-specific transfer guidelines.

Impact of transfer time on pregnancy outcomes in frozen-embryo transfer cycles.

OBJECTIVE: To identify the impact of embryo transfer time (total seconds from the loading of the transfer catheter to the expulsion of the embryo(s) into the uterine cavity) on clinical pregnancy (CPR), implantation (IR), and live birth (LBR) rates. DESIGN: Retrospective cohort study. SETTING: Academic hospital practice. PATIENT(S): A total of 465 women undergoing 571 frozen-embryo transfers with the use of cryopreserved blastocysts in a single academic institution from 2007 through 2014. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): CPR, IR, and LBR. RESULT(S): The cohort was divided into tertiles according to transfer time in seconds (T1: 33-55; T2: 57-81; T3: 82-582) with mean (SD) transfer times of 47.4 (5.7), 67.1 (7.3), and 121.9 (55.1) seconds, respectively. Crude CPRs were 43.9%, 48.7%, and 48.7% among the respective tertiles, crude IRs were 36.9%, 39.9%, and 38.6%, and crude LBRs were 34.8%, 39.6%, and 36.0%. In univariate analysis, inferior cohort score, blood inside catheter, difficult mock transfer, and use of an outer sheath were negatively associated with CPR. No association was seen between physician performing the transfer (including fellows) and CPR. In multivariate regression, longer transfer time was not associated with CPR. With T1 as reference, adjusted odds ratios (95% confidence interval) were 1.28 (0.77-2.11) and 1.52 (0.85-2.71) for transfer time groups T2 and T3, respectively. CONCLUSION(S): After adjusting for potential confounders, this analysis found that contrary to commonly held belief, longer embryo transfer times do not negatively affect CPR, IR, or LBR.

Total number of oocytes and zygotes are predictive of live birth pregnancy in fresh donor oocyte in vitro fertilization cycles.

OBJECTIVE: To evaluate the association of oocyte donor-recipient characteristics, oocyte donor response, and live birth pregnancy rate following fresh donor oocyte IVF-ET. DESIGN: Retrospective cohort study. SETTING: Academic reproductive medicine practice. PATIENT(S): Two hundred thirty-seven consecutive fresh donor oocyte IVF-ET cycles from January 1, 2007 to December 31, 2013 at the Massachusetts General Hospital Fertility Center. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth rate per cycle initiated. RESULT(S): The mean (±SD) age of oocyte donors and recipients was 27.0 ± 3.7 and 41.4 ± 4.6 years, respectively. Oocyte donor demographic/reproductive characteristics, ovarian reserve testing, and peak serum E2 during ovarian stimulation were similar among cycles which did and did not result in live birth, respectively. Overall implantation, clinical pregnancy, and live birth pregnancy rates per cycle initiated were 40.5%, 60.8%, and 54.9%, respectively. The greatest probability of live birth was observed in cycles with >10 oocytes retrieved, mature oocytes, oocytes with normal fertilization (zygote-two pronuclear stage), and cleaved embryos. CONCLUSION(S): The number of oocytes (total and mature), zygotes, and cleaved embryos are associated with live birth following donor oocyte IVF cycles. These findings suggest that specific peri-fertilization factors may be predictive of pregnancy outcomes following donor oocyte IVF cycles.

Preconceptional thyroid-stimulating hormone levels and outcomes of intrauterine insemination among euthyroid infertile women.

OBJECTIVE: To evaluate differences in intrauterine insemination (IUI) outcomes among euthyroid women with preconceptional thyroid-stimulating hormone (TSH) values in the normal (0.4-2.4 mIU/L) and high-normal (2.5-4.9 mIU/L) ranges. DESIGN: Cohort study. SETTING: A single fertility center. PATIENT(S): A total of 1,477 women who underwent 4,064 IUI cycles between the years 2004 and 2012. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth, clinical pregnancy, spontaneous abortion (SAB), and IUI cycle parameters. RESULT(S): Cycles were categorized into 4 groups based on preconceptional TSH values: 0.40-1.36 mIU/L; 1.37-1.86 mIU/L; 1.87-2.49 mIU/L; and 2.50-4.99 mIU/L. No statistically significant differences were found in IUI cycle parameters, clinical pregnancy rates, or live births per initiated cycle among the 4 TSH groups. However, preconceptional TSH was inversely related to SAB and positively related to live birth among women who achieved a clinical pregnancy. In this group of women, cycles with TSH values between 2.5 and 4.9 mIU/L were related to lower odds of SAB (odds ratio: 0.32; 95% confidence interval: 0.16-0.65) and higher odds of live birth (odds ratio: 2.80; 95% confidence interval: 1.43-5.48) compared with cycles among women in the lowest TSH group. CONCLUSION(S): Among euthyroid patients, preconceptional TSH values in the high-normal range (between 2.5 and 4.9 mIU/L) are not associated with adverse IUI outcomes.

MicroRNAs in the development and pathobiology of uterine leiomyomata: does evidence support future strategies for clinical intervention?

BACKGROUND: Human leiomyomata (fibroids) are benign tumors of the uterus, represent the most common neoplasms of reproductive-aged women and have a prevalence of ∼70% in the general population. This disorder conveys a significant degree of morbidity and remains the leading indication for hysterectomy in the USA. Prior investigations of aberrant microRNA (miRNA) expression in various malignancies have provided invaluable insight into the role of this class of small non-coding RNAs in tumor growth. Evidence of irregular miRNA expression in uterine fibroids has garnered recent interest for diagnostic and therapeutic applications. Since miRNA gene targets modulate several processes implicated in the genesis of uterine fibroids, more focused investigation has the potential to elucidate the functional significance of miRNA in the genesis and pathology of the disease. METHODS: Comprehensive electronic searches of peer reviewed published literature in PubMed (US National Library of Medicine, National Institute of Health; http://www.ncbi.nlm.nih.gov/pubmed/) were performed for content related to the biologic functions of miRNA, the roles of miRNA in human disease and studies investigating miRNA in the context of uterine leiomyomata. Herein, this article will review the current evidence supporting the use of miRNA expression profiling as an investigative tool to assess the pathobiology of uterine fibroids and will discuss potential future applications of miRNAs as biomarkers and therapeutic targets. RESULTS: Mounting evidence supports a functional role for miRNA as either indirect or direct regulators of gene expression which impacts the pathobiology of uterine fibroids. Specifically, miRNAs let-7, 200a, 200c, 93, 106b and 21 have been implicated in cellular proliferation, apoptosis, extracellular matrix turnover, angiogenesis and inflammation. Preliminary data provide evidence to suggest that respective in vitro miRNA expression in leiomyomata and myometrium is regulated by sex steroids. CONCLUSIONS: Collectively, the identification of aberrantly expressed miRNAs in uterine leiomyomata and accumulating data derived from mining of gene target prediction models and recent functional studies support the concept that miRNAs might impact the genesis and progression of disease. However, the specific biologic functions of differential miRNA expression have yet to be confirmed in vivo. Further functional studies and developing miRNA technology may provide the basis for future applications of miRNAs in clinical medicine as biomarkers and therapeutic targets.