Antimullerian hormone levels and numbers and sizes of antral follicles in regularly menstruating women of reproductive age referenced to true ovulation day

Objective: To assess menstrual cycle antimullerian hormone (AMH) levels in reproductive age women and which/how many follicles substantially produce AMH. Design: Prospective study of menstruating women using mixed-effects models to analyze AMH variability and correlation of follicle counts/size classes to AMH levels. Setting: Clinic. Patient(s): Regular menstruating women with ovulatory cycles (n = 40, aged 18-37 years) and no known subfertility. Intervention(s): Women collected daily urine samples and visited the study center for blood samples/transvaginal ultrasound during one complete menstrual cycle (visits were every 2 days; daily from follicle size >16 mm until postovulation). Main Outcome Measure(s): AMH levels throughout the menstrual cycle, correlated with antral follicles as observed by ultrasound and identification of follicles producing AMH. Results: Of all antral follicles visible by high-resolution ultrasound, AMH is produced substantially only by follicles up to 7 mm in diameter. For women with basal AMH >1 ng/mL, mean AMH concentrations vary across ovulatory menstrual cycles, showing a statistically significant decrease from -5 to 2 days after objective ovulation; significantly lower mean luteal AMH levels (-7.59% to mean follicular AMH) are detected. The number of antral follicles can be estimated from AMH (ng/mL) levels using the modified Beckman Coulter Generation II AMH assay for any day of the follicular phase. Conclusion(s): AMH concentrations vary across ovulatory menstrual cycles, showing a significant periovulatory decrease. The number of small antral follicles can be estimated from preovulatory AMH levels with relevance for patient management. (C) 2015 by American Society for Reproductive Medicine

Monitoring the menstrual cycle: Comparison of urinary and serum reproductive hormones referenced to true ovulation

Objective The aim of the study was to examine relationships and interindividual variations in urinary and serum reproductive hormone levels relative to ultrasound-observed ovulation in menstrual cycles of apparently normally menstruating women.Methods This was a prospective study of normally menstruating women (no known subfertility), aged 18-40 years (n = 40), who collected daily urine samples and attended the study centre for blood samples and transvaginal ultrasound during one complete menstrual cycle. Serum luteinising hormone (LH), progesterone, estradiol, urinary LH, pregnanediol-3- glucuronide (P3G) and estrone-3-glucuronide were measured. Ultrasound was conducted by two physicians and interpreted by central expert review.Results Menstrual cycle length varied from 22 to 37 days (median 27 days). Ovulation by ultrasound ranged from day 8 to day 26 (median day 15). Serum and urinary hormone profiles showed excellent agreement. Estrogen and LH hormone peaks in urine and serum showed a range of signal characteristics across the study group before and after ovulation. The rise in estrogen and LH always occurred before ovulation; the progesterone rise from baseline always occurred after ovulation.Conclusions Urinary and serum reproductive hormones showed excellent agreement and may be used interchangeably. The beginning of the surge in serum and urinary LH was an excellent predictor of ovulation. The rise in progesterone and P3G above baseline was a consistent marker of luteinisation confirming ovulation. Both LH and progesterone surges delivered clear, sharp signals in all volunteers, allowing reliable detection and confirmation of ovulation

Impact of sperm cell source on the results of intracytoplasmic sperm injection

There is an ongoing debate whether the source of sperm cells, the etiology or the extent of male factor infertility has influence on the outcome of ICSI cycles. The results of intracytoplasmic sperm injection (ICSI) according to the source of spermatozoa in patients with severe male factor infertility were compared in a retrospective study: 249 couples underwent a total of 337 fresh ICSI cycles with the use of fresh motile testicular or fresh motile ejaculated spermatozoa. For all variables, there were no statistically significant differences in the ICSI results between both groups. Fertilization rates were 46.8 % for testicular and 47.6 % for ejaculated spermatozoa. Live birth rates per embryo transfer were 20.4 % using testicular spermatozoa and 22.8 % using ejaculated spermatozoa. Neither the source of spermatozoa nor the etiology of severe male infertility has relevant impact on the results of ICSI cycles as long as fresh motile, morphologically normal spermatozoa are used. Therefore, in case of cryptozoospermia, we recommend to preferentially use ejaculated spermatozoa to prevent those men from an unnecessary testicular biopsy avoiding risks and costs implied

<i>FTO</i> Is Associated with Aortic Valve Stenosis in a Gender Specific Manner of Heterozygote Advantage: A Population-Based Case-Control Study

<div><p>Background</p><p>Single nucleotide polymorphisms (SNPs) within the <i>Fat mass and obesity associated</i> (<i>FTO</i>) gene have been linked with increased body weight. However, the data on an association of <i>FTO</i> with cardiovascular diseases remains conflicting. Therefore, we ascertained whether <i>FTO</i> is associated with aortic valve stenosis (AVS), one of the most frequent cardiovascular diseases in the Western world.</p><p>Methods and Findings</p><p>In this population-based case-control study the <i>FTO</i> SNP rs9939609 was analyzed in 300 German patients with AVS and 429 German controls of the KORA survey S4, representing a random population. Blood samples were collected prior to aortic valve replacement in AVS cases and <i>FTO</i> rs9939609 was genotyped via ARMS-PCR. Genotype frequencies differed significantly between AVS cases and KORA controls (<i>p</i> = 0.004). Separate gender-analyses uncovered an association of <i>FTO</i> with AVS exclusively in males; homozygote carriers for the risk-allele (A) had a higher risk to develop AVS (<i>p</i> = 0.017, odds ratio (OR) 1.727; 95% confidence interval (CI) 1.087–2.747, recessive model), whereas heterozygote carriers for the risk-allele showed a lower risk (<i>p</i> = 0.002, OR 0.565, 95% CI 0.384–0.828, overdominant model). After adjustment for multiple co-variables, the odds ratios of heterozygotes remained significant for an association with AVS (<i>p</i> = 0.008, OR 0.565, 95% CI 0.369–0.861).</p><p>Conclusions</p><p>This study revealed an association of <i>FTO</i> rs9939609 with AVS. Furthermore, this association was restricted to men, with heterozygotes having a significantly lower chance to develop AVS. Lastly, the association between <i>FTO</i> and AVS was independent of BMI and other variables such as diabetes mellitus.</p></div

Relationship between anti-Mullerian hormone and antral follicle count across the menstrual cycle using the Beckman Coulter Access assay in comparison with Gen II manual assay

Background: The study aim was to validate Beckman Coulter's fully automated Access Immunoassay System (BC Access assay) for anti-Mullerian hormone (AMH) and compare it with Beckman Coulter's Modified Manual Generation II assay (BC Mod Gen II), with regard to cycle AMH fluctuations and antral follicle counts. Methods: During one complete menstrual cycle, transvaginal ultrasound was performed on regularly menstruating women (n = 39; 18-40 years) every 2 days until the dominant ovarian follicle reached 16 mm, then daily until observed ovulation; blood samples were collected throughout the cycle. Number and size of antral follicles was determined and AMH levels measured using both assays. Results: AMH levels measured by the BC Access assay vary over ovulatory menstrual cycles, with a statistically significant pre-ovulatory decrease from -5 to +2 days around objective ovulation. Mean luteal AMH levels were significantly lower (- 7.99%) than mean follicular levels but increased again towards the end of the luteal phase. Antral follicle count can be estimated from AMH (ng/mL, BC Access assay) concentrations on any follicular phase day. BC Access assay-obtained AMH values are considerably lower compared with the BC Mod Gen II assay (- 19% on average); conversion equation: AMH BC Access (ng/mL) = 0.85 [AMH BC Mod Gen II (ng/mL)](0.95). Conclusions: AMH levels vary throughout the cycle, independently of assay utilised. A formula can be used to convert BC Access assay-obtained AMH levels to BC Mod Gen II values. The number of antral follicles can be consistently estimated from pre-ovulatory AMH levels using either assay

Odds Ratios (OR) and 95% Confidence Intervals (CI) of <i>FTO</i> rs9939609 Between Male AVS Cases and KORA Controls.

<p>¹Values were adjusted for age, BMI, diabetes mellitus and hypertension.</p><p>Odds Ratios (OR) and 95% Confidence Intervals (CI) of <i>FTO</i> rs9939609 Between Male AVS Cases and KORA Controls.</p

Demographic and Clinical Data of AVS Cases and KORA Controls.

<p>Two-sided <i>p</i>-values were calculated using</p><p>¹Fisher’s-Exact-Test</p><p>²Mann-Whitney-U Test and</p><p>³Student’s t-Test. Values are mean±SD. PAD, peripheral artery disease.</p><p>Demographic and Clinical Data of AVS Cases and KORA Controls.</p