Grzegorz Jakiel

Use of ovarian reserve parameters for predicting live births in women undergoing in vitro fertilization

OBJECTIVE To examine common clinical determinants, including patient age; levels of anti-Müllerian hormone (AMH), inhibin B, and follicle-stimulating hormone (FSH); antral follicle count (AFC); and number of oocytes retrieved, to predict live births in women undergoing in vitro fertilization. STUDY DESIGN Women undergoing cycles of intracytoplasmic sperm injection (ICSI) for the first time were reviewed retrospectively, and serum levels of AMH, inhibin B, and FSH, as well as AFC (days 1 and 4 of pre-ICSI menstrual period) and patient age were analyzed as determinants of live birth rates. RESULTS Of the patients studied, 35.71% (891/2495) became pregnant, with live births achieved in 32.20% (806/2495) of cycles initiated and in 46.37% (806/1738) of embryo transfers. Clinical pregnancy rate was 35.71% (891/2495) for cycles initiated and 51.26% (891/2318) for embryo transfers. Univariate analysis revealed that the odds of live birth significantly decreased with increasing age, declining AMH or inhibin B concentrations, and fewer oocytes retrieved. At AMH levels greater than 5.7 ng/ml, the odds of live birth were 3.18 times greater than for AMH levels less than 1.9 ng/ml [95% confidence interval (CI), 1.89-5.43]. Using multivariate logistic regression, only AMH (OR = 1.89; 95% CI, 1.00-3.60; p < 0.05) and AFC (OR = 1.86; 95% CI, 1.02-3.40; p < 0.05) showed statistically significant associations with live birth. Area under the curve for ROC (ROC(AUC)) indicated that AMH (AUC = 0.60) surpassed AFC (AUC = 0.59), number of oocytes retrieved (AUC = 0.59), inhibin B (AUC = 0.55), FSH (ROC(AUC) = 0.54) and chronological age (ROC(AUC) = 0.53) in predicting live birth. CONCLUSIONS In this assessment of various indices (i.e., age; levels of AMH, inhibin B, and FSH; AFC; and quantity of oocytes retrieved) for predicting live births for IVF patients, AMH, AFC and the quantity of oocytes retrieved constituted the most reliable determinants.

Probability of live birth in women with extremely low anti-Müllerian hormone concentrations

The aim of the present study was to investigate the clinical pregnancy and live birth rates in women with extremely low (≤ 0.4 ng/ml) anti-Müllerian hormone (AMH) concentrations. The study included 101 women (188 cycles) with extremely low AMH concentrations undergoing IVF cycles and compared the number of live births in women with low AMH. Moreover, the study compared the number of live births in women with or without endometriosis stage III/IV. Fourteen clinical pregnancies and 14 live births (including one pair of twins) were recorded; one woman miscarried. Significantly higher clinical pregnancy (P = 0.046) and live birth rates (P = 0.018) were found in women aged < 35 years compared with older women. AMH concentration did not differ significantly between women with or without endometriosis and there were six live births in women with endometriosis. This was not significantly different from the rate in healthy women. It is concluded that live births are possible in women with extremely low AMH concentrations. The presence of endometriosis stage III/IV did not affect live birth rates in women with extremely low AMH concentrations although an important limitation of the study is the small number of women included who were affected by that disease.

Anti-Müllerian hormone (AMH) is a strong predictor of live birth in women undergoing assisted reproductive technology.

In the present study, we evaluated the clinical value of the following parameters: basal anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin B and antral follicle count (AFC) in predicting live birth outcomes. The study involved 603 women undergoing in vitro fertilization (IVF) using the long protocol for controlled ovarian hyperstimulation (COH). Serum levels of AMH, FSH and inhibin B as well as AFC were measured on the first three days of the menstrual cycle prior to the beginning of stimulation. AMH was the only independent parameter that correlated with the chance of live birth. We found that live birth rates of 46.2% (patient age <35 years), 44.7% (35-37 years), 32.1% (38-39) and 15.3% (>39) were associated with concentrations of AMH>1.4 ng/ml. For the AMH range 0.6-1.4 ng/ml, the live birth rates were 29.3%, 12.5%, 5.6% and 2.7%, respectively, and for AMH concentrations below 0.6 ng/ml the rates were 7.1%, 8.3%, 0% and 5.8%, respectively. Independently of other parameters affecting the chance of live birth, the success rate was the highest when the AMH level was >2 ng/ml, significantly lower when the AMH concentration was about 1 ng/ml, and 0% when the AMH concentration was ∼0.1 ng/ml. In conclusion, this is the first report to demonstrate that AMH level correlated better than age, FSH or inhibin B concentrations or AFC with live birth outcome. Therefore, the basal serum concentration of AMH may become a new, substantial prognostic factor regarding live birth above and beyond other currently available predictors of IVF outcome.

Decreasing quality of the new generations of anti-Mullerian hormone assays.

Anti-Müllerian hormone (AMH) measurements are widely used to optimize the stimulation protocols. First generation AMH kits correlated well with ovarian reserve and response to stimulation. In the present study we aimed to asses if the new generation kits share the same accurate correlations. Retrospective data were collected from 8323 blood samples. For comparison we used Immunotech I generation kit (ImI 4035 samples), Beckman Coulter II generation kit RUO (BCII RUO 3449, samples) and Beckman Coulter II generation kit with IVD certificate (BCII IVD 839 samples). We compared average AMH concentrations measured with different kits, as well as correlation between kits. We also compared average AMH concentrations in sera collected on different cycle days and samples of different quality of preservation. AMH serum concentrations differed for each kit, ranging 4.4 ± 4.12 (mean ± SD) for the ImI, 2.68 ± 3.15 for the BCII RUO, and 1.64 ± 2.85 for BCII IVD. The mean differences from an adjusted regression model were −48.7%, −40%, and −69.2%, respectively. In conclusion, the changes of the BC AMH kits are unpredictable; however, the improvement of them is still possible. It would be very dangerous to use elaborated stimulation protocol (based on the Ist generation AMH results) with the results from the IInd generation assays.

Prenatal diagnosis of congenital myopathies and muscular dystrophies

Congenital myopathies and muscular dystrophies constitute a genetically and phenotypically heterogeneous group of rare inherited diseases characterized by muscle weakness and atrophy, motor delay and respiratory insufficiency. To date, curative care is not available for these diseases, which may severely affect both life‐span and quality of life. We discuss prenatal diagnosis and genetic counseling for families at risk, as well as diagnostic possibilities in sporadic cases.

The role of vitamin D in reproductive dysfunction in women – a systematic review

Vitamin D is essential for the proper functioning of the human body. There is also evidence of its strong association with fertility problems in women. This review aims to evaluate the relationship between vitamin D and diseases affecting womens fertility (polycystic ovarian syndrome (PCOS), uterine leiomyomas and endometriosis), and in vitro fertilization (IVF) outcome. A systematic review of the literature was conducted in Scopus and PubMed for relevant English language publications since 1989. Vitamin D influences the functioning of the reproductive system in women and has been associated with PCOS, uterine leiomyomas, endometriosis and in vitro fertilization (IVF) outcome. However, further studies on larger groups of patients are needed to establish what role vitamin D plays in the treatment of female infertility.

Next generation sequencing for preimplantation genetic testing of blastocysts aneuploidies in women of different ages.

Most of the current preimplantation genetic screening of aneuploidies tests are based on the low quality and low density comparative genomic hybridization arrays. The results are based on fewer than 2,700 probes. Our main outcome was the association of aneuploidy rates and the womens age. Between August-December 2013, 198 blastocysts from women (mean age 36.3+-4.6) undergoing in vitro fertilization underwent routine trophectoderm biopsy. NGS was performed on Ion Torrent PGM (Life Technologies). The results were analyzed in five age groups (<31, 31-35, 36-38, 39-40 and >40). 85 blastocysts were normal according to NGS results. The results in the investigated groups were (% of normal blastocyst in each group): <31 (41.9%), 31-35 (47.6%), 36-38 (47.8%), 39-40 (37.7%) and >40 (38.5%). Our study suggests that NGS PGD is applicable for routine preimplantation genetic testing. It allows also for easy customization of the procedure for each individual patient making personalized diagnostics a reality.

Difficulties in adaptation to pregnancy following natural conception or use of assisted reproduction techniques: a comparative study.

Background To evaluate the influence assisted reproduction techniques (ARTs) may have on womens adaptation to resulting pregnancies. Methods Retrospective assessment of how women adapt to their pregnancies following ART. A questionnaire was used that ranked their attitudes according to the 5-grade Likert scale. The study included 250 women who gave birth to their first child. Of these pregnancies, 125 had been obtained by means of ART; the remaining 125 were naturally conceived. Results Difficulties in adaptation to pregnancy were significantly more frequent in women whose pregnancies resulted from the use of ARTs than in those who had conceived naturally (p = 0.000005). The subjects in the first group were significantly older (p = 0.04), more affluent (p = 0.000005) and had more frequently interrupted their professional work than women in the latter group. The two groups did not differ with regard to frequency of hospitalisations. Conclusions ART significantly increases difficulties in adaptation to resulting pregnancies. The main factors responsible for these difficulties are age, socio-economic conditions and interruption of professional activity.

Targeted prenatal diagnosis of Pallister–Killian syndrome

To present five new cases of prenatally diagnosed Pallister–Killian syndrome (PKS) and to propose an approach for a targeted diagnosis.

Oxidative stress and total antioxidant status in term newborns and their mothers

UNLABELLED The peripartum period and delivery are considered critical for maintaining a balance between the production of free oxygen radicals and functional incompetence of the antioxidant system of a foetus and a neonate. OBJECTIVE The aim of the study was to evaluate the oxidoreductive state of mothers and their newborns immediately after delivery and in the first few days after birth. METHOD Eighty-five mothers and their healthy, term newborns were included into the prospective study. Total antioxidant capacity (TAC) and thiobarbituric acid reactive substances (TBARS) in maternal placenta and milk, as well as blood and urine of the neonates on the first and third day after birth, were examined. RESULTS Elevated levels of TBARS were found in maternal placenta and neonatal blood on the third day after birth, but low concentrations were observed in maternal milk. On the contrary, total antioxidant status (TAS) showed a declining tendency in neonatal blood and an increasing tendency in breast milk. Markers of oxidative stress and antioxidant capacity were independent of the mode of delivery. CONCLUSIONS Values of oxidative stress markers in mothers and newborns immediately after birth were elevated and increased further during the first few days of neonatal life. Breast milk was the only nutritional substance with high antioxidant activity. At the same time, TBARS levels in breast milk decreased, which might indicate its protective role in reducing oxidative stress in newborns.