Possible risk for cancer among children born following assisted reproductive technology in Israel.

BACKGROUND: Among children conceived by assisted reproductive technology (ART), increased risk of adverse birth outcomes has been observed, including multiple births, preterm births, and congenital malformations. Regarding cancer among ART-conceived children, findings are discrepant. METHODS: This is a historical cohort of 9,042 ART-conceived children and 211,763 spontaneously conceived (SC) children born from 1997 through 2004. The median duration of follow-up was 10.6 years (interquartile range 9.0-12.3) in the ART group and 9.3 years (interquartile range 8.0-10.6) in the SC group. The cohort database was linked with the Israel National Cancer Registry updated until December 31, 2011 using each child's personal identification number. RESULTS: Twenty-one cases of cancer were identified in the ART group (2.2 per 10,000 person-years), as compared to 361 cancer cases in the SC group (1.8 per 10,000 person-years). The relative risk (RR) for overall cancer in the ART group compared to the SC group adjusted for maternal characteristics was 1.18 (95% confidence interval [CI] 0.80-1.75). ART children had a significantly increased risk for specific cancers, although based on small number of cases, including two cases of retinoblastoma (RR 6.18, 95% CI 1.22-31.2), as well as four cases of renal tumors (RR 3.25, 95% CI 1.67-6.32). CONCLUSION: A statistically significant increased risk for two pediatric cancers was found. However, for overall types of cancer the risk estimate was elevated but not statistically significant. Further studies with larger sample size and longer follow-up time are warranted in order to either confirm or refute these findings.

The effect of ozonated sterile saline irrigation on the endometrium - A preliminary study.

The objective of this study was to evaluate the effect of sterile ozonated saline endometrial irrigation on sonographic and histological endometrial parameters. This prospective investigation was performed in 12 healthy, ovulating women over three consecutive menstrual cycles: control cycle (endometrial irrigation with 10 cc of normal saline at day 10), no intervention cycle and study cycle (irrigation with 10 cc of sterile ozonated saline at day 10). Endometrial thickness was measured by transvaginal ultrasound at days 10 and 12 of the control and study cycles, and endometrial samplings were obtained from the participants two days after the irrigations (i.e. on day 12) for histological evaluation. Ozonated saline irrigation, compared to normal saline irrigation, resulted in a statistically significant elevation of the columnar epithelial height (30.30 ± 3.04 vs. 25.82 ± 3.28 µm, p < 0.003), increased number of endometrial blood vessels (30.48 ± 11.38 vs. 19.12 ± 8.74, p < 0.005) and increased number of stromal cells (191.30 ± 34.40 vs. 151.29 ± 29.98, p < 0.01). In conclusion, sterile ozonated saline irrigation of the endometrium has a significant favourable effect on various histological endometrial parameters. Further studies are needed to evaluate the effect of these changes on endometrial receptivity and pregnancy rates.

The effect of LH rise during artificial frozen-thawed embryo transfer (FET) cycles.

PURPOSE: To evaluate the association between a rise in serum luteinizing hormone (LH) levels during artificial frozen-thawed embryo transfer (FET) cycles and clinical pregnancy rate. METHODS: A retrospective cohort study of women undergoing artificial FET cycles. We compared cycles in which LH double itself from the early follicular phase and further (group A) to cycles without a rise in LH (group B). Endometrium preparation was achieved by administration of 2 mg three times per day estradiol valerate tablets. Embryo transfer (ET) was conducted after achieving endometrial thickness > 7 mm and vaginal progesterone was added according to the embryo's age. A beta-hCG was measured 13-14 days after ET. Clinical pregnancy was diagnosed on transvaginal ultrasound. RESULTS: Data from 984-FET cycles were retrieved. LH, exogenous estradiol (E2), progesterone values, endometrial thickness, and pregnancy outcomes were available in all patients. From 984-FET cycles, 629 (63.9%) had a doubling, and 355 (36.07%) had no rise in LH. Patients mean age was 30 years, similar in both groups. A multivariable logistic regression analysis was calculated to assess the effect of LH rise and pregnancy outcomes, after adjusting for confounders including a rise in E2 level and endometrial thickness. In this model, there was no association between doubling LH values and pregnancy rates (adjusted odds ratio: 1.06, 95% CI: 0.75-1.5, P = 0.74). CONCLUSION: LH rise during artificial FET cycles does not alter pregnancy rates. Apparently, hormonal monitoring of LH levels may not yield useful information in the artificial FET cycle and may be omitted. LAY SUMMARY: Supplementation of estradiol, a hormone produced by the ovaries, starting at the beginning of the menstrual cycle of an artificially frozen embryo transfer (FET) can lead to a rise in luteinizing hormone (LH), the hormone that induces ovulation. Such a rise in LH may interfere with embryo implantation, the process where the embryo attaches to the inner lining of the uterus and, therefore, could affect the chances of pregnancy. The current study is the first to assess the effect of a dynamic rise in LH levels during FET cycles on pregnancy rates. This study found no difference in pregnancy rates between FET cycles where the LH doubled compared to cycles without such a rise in LH. Larger, prospective studies should be conducted to assess the impact of LH elevation on pregnancy outcomes.

Modulation of heart rate variability by estrogen in young women undergoing induction of ovulation.

Estrogens are involved in the modulation of the cardiovascular system, yet their effects in young women remains largely unknown. Women who undergo ovulation induction treatments attain extremely high estrogen concentrations during a very short time period. The aim of the present study was to evaluate the effects of an acute increase in estrogens on the autonomic nervous system modulation of heart rate variability (HRV). A total of 27 women undergoing ovulation induction and 14 normally menstruating women were prospectively studied. HRV was assessed during nadir and peak estrogen using time domain and power spectral density analyses. A significant increase in high-frequency spectral power (243 +/- 77 vs. 188 +/- 73 ms(2)/Hz, P < 0.01) with a significant decrease in the ratio of low to high-frequency power was observed during estrogen peak in women undergoing induction of ovulation. The acute increase in estrogen in women undergoing ovulation induction was associated with vagal activation and altered sympathovagal balance.

Can myometrial electrical activity identify patients in preterm labor?

OBJECTIVE: The objective of the study was to determine whether myometrial electrical activity can differentiate false from true preterm labor. STUDY DESIGN: Electrical uterine myography (EUM) was measured prospectively on 87 women, gestational age less than 35 weeks. The period between contractions, power of contraction peaks and movement of center of electrical activity (RMS), was used to develop an index score (1-5) for prediction of preterm delivery (PTD) within 14 days of the test. The score was compared with fetal fibronectin (fFN) and cervical length (CL). RESULTS: Patients delivering within 14 days from testing showed a higher index and mean RMS (P = .000). No patients with EUM index scores of 1-2 delivered in this time frame. Combining EUM with CL or fFN increased predictability. Logistic regression revealed that history of PTD and EUM index had 4- to 5-fold increased risk for PTD. Gestational age at testing, body mass index, fFN, and CL were nonsignificant contributors to PTD risk. CONCLUSION: Measuring myometrial electrical activity may enhance identification of patients in true premature labor.

Subendometrial arterial spectral doppler assessment during IVF cycles and its correlation with treatment outcome.

The influence of blood flow impedance in subendometrial arteries on embryo implantation rate was investigated by transvaginal sonographic examination in in vitro fertilization (IVF) cycles. A total of 39 women undergoing IVF treatment were evaluated along the treatment cycle. Power and spectral Doppler studies of subendometrial arteries were performed to calculate the pulsatility index (PI), resistance index (RI) and systolic:diastolic ratio (S:D). The correlation between these parameters and pregnancy achievement was analyzed. Patients were grouped according to whether pregnancy was achieved or not. RI and S:D did not differ between the groups along the course of treatment. In pregnant patients, the PI was significantly lower in the beginning of the cycle than on the preovulation day and ovum pickup day. PI in the beginning of the treatment was significantly lower in pregnancy cycles than in nonpregnancy ones. A lower PI on day 1 was correlated with a better chance for pregnancy.