Einat Shalom-Paz

Age-related normograms of serum antimüllerian hormone levels in a population of infertile women: a multicenter study

OBJECTIVE To produce age-related normograms for serum antimüllerian hormone (AMH) level in infertile women without polycystic ovaries (non-PCO). DESIGN Retrospective cohort analysis. SETTING Fifteen academic reproductive centers. PATIENT(S) A total of 3,871 infertile women. INTERVENTION(S) Blood sampling for AMH level. MAIN OUTCOME MEASURE(S) Serum AMH levels and correlation between age and different percentiles of AMH. RESULT(S) Age-related normograms for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles of AMH were produced. We found that the curves of AMH by age for the 3rd to 50th percentiles fit the model and appearance of linear relation, whereas the curves of >75th percentiles fit cubic relation. There were significant differences in AMH and FSH levels and in antral follicle count (AFC) among women aged 24-33 years, 34-38 years, and ≥39 years. Multivariate stepwise linear regression analysis of FSH, age, AFC, and the type of AMH kit as predictors of AMH level shows that all variables are independently associated with AMH level, in the following order: AFC, FSH, type of AMH kit, and age. CONCLUSION(S) Age-related normograms in non-PCO infertile women for the 3rd to 97th percentiles were produced. These normograms could provide a reference guide for the clinician to consult women with infertility. However, future validation with longitudinal data is still needed.

Promoting implantation by local injury to the endometrium.

OBJECTIVE To evaluate the association between endometrial injury, implantation and pregnancy rate. DESIGN We performed a literature search using the keywords endometrial injury, local endometrial injury, endometrial biopsy, endometrial receptivity, implantation, in vitro fertilization, and implantation failure and conducted the search in Medline, EMBASE, and Cochrane Database of systematic reviews. SETTING None. PATIENT(S) None. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) None. RESULT(S) Clinical and basic science data regarding the association between endometrial injury and improved implantation rate are limited. However, current evidence suggests that endometrial injury before IVF among women with previous repeated IVF failure is associated with increased rates of implantation, clinical pregnancy, and live birth. CONCLUSION(S) Endometrial injury may have a beneficial role in implantation and improve the pregnancy rate. However, there are still many unanswered question including patients selection, timing, technique and number of endometrial biopsies needed.

Placenta weight percentile curves for singleton and twins deliveries

OBJECTIVE To establish updated placental percentile nomograms in a large North American population for singleton and twin gestations for the use of researchers and clinicians. STUDY DESIGN Data was extracted from our computerized registry; McGill Obstetrics and Neonatal Database (MOND). The registry includes all the obstetrical data on all deliveries at the McGill University, including placental weight, placental pathologies, maternal and perinatal complications. 20,635 singleton deliveries and 527 twin deliveries were included. Placental weight, gestational age at delivery, birth weight and gender were retrieved. Tables and figures for the 3rd,10th,25th, 50th, 75th 90th, and 97th percentile of placental weight by gestational age, placental weight by birth weight and placental to birth weight ratio by gestational age were produced. RESULTS Tables and figures are presented for placental percentiles curves according to gestational age, gestational weight and gender for singleton and twin deliveries. In addition, tables and figures are presented for the ratio of placental weight to birth weight. CONCLUSIONS Population percentile curves have been produced for placental weight and for the ratio of placental weight to birth weight to for singleton and twin deliveries.

Fertility preservation for breast-cancer patients using IVM followed by oocyte or embryo vitrification.

Unstimulated in-vitro maturation (IVM) cycles are considered for fertility preservation in breast cancer due to avoidance of ovarian stimulation and shortened time to oocyte retrieval. This study evaluated the efficacy of this approach in a retrospective cohort analysis of 66 patients with breast cancer. Immature oocytes were collected and matured in vitro and then either vitrified or fertilized and preserved as vitrified embryos. In group 1 (vitrified oocytes, n=35), the average number of oocytes retrieved was 11.4 ± 8.8, the maturation rate was 64.2% and an average of 7.9 ± 6.6 oocytes were vitrified per patient treated. The median duration from the first evaluation to oocyte retrieval was 8 days. In group 2 (vitrified embryos, n=31) the average number of oocytes retrieved was 9.7 ± 6.4, the maturation rate was 53.2% and an average of 5.8 ± 2.7 mature oocytes were available for fertilization/patient. The fertilization rate was 77.8%, resulting in 4.5 ± 2.7 vitrified embryos/patient. The median duration from the first evaluation to oocyte retrieval was 13 days. Calculated pregnancy rates per vitrified oocyte and embryo were 3.8% and 8.1%, respectively. IVM can be considered a useful option for fertility preservation in breast-cancer patients.

Effects of excision of ovarian endometrioma on the antral follicle count and collected oocytes for in vitro fertilization

We compared the response of operated and nonoperated ovaries to gonadotropin stimulation in 38 women who had had excision of ovarian endometrioma. The antral follicle count, numbers of dominant follicles, and number of oocytes collected in the operated ovaries were significantly lower than in the nonoperated ovaries suggesting reduced ovarian reserve after excision of ovarian endometrioma.

Age-related normogram for antral follicle count: McGill reference guide

OBJECTIVE To produce age-related normograms for antral follicle count in an infertile population without polycystic ovaries. DESIGN Retrospective cohort analysis. SETTING University teaching center. PATIENT(S) Eighteen hundred sixty-six infertile patients. INTERVENTION(S) Baseline transvaginal ultrasound examination between days 2 and 4 of the menstrual cycle. MAIN OUTCOME MEASURE(S) Correlation between age and different percentiles of antral follicle count. RESULT(S) The age-related normogram for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentile of antral follicle count showed a biphasic mode of antral follicle count decline with two different rates of antral follicle count loss: a steep-slope phase (high rate of antral follicle count loss) and a moderate-slope phase (restrained rate of antral follicle count losses). In the low antral follicle count percentiles (3rd, 10th, 25th), the phase of high loss rate of follicles preceded the phase of slow loss rate, whereas in the high antral follicle count percentiles (75th, 90th, 97th) the opposite was found. CONCLUSION(S) Age-related normograms in infertile women without polycystic ovaries demonstrate a biphasic pattern of decreased antral follicles. These normograms could provide a reference guide for the clinician in consulting with women with infertility. However, future validation with longitudinal data is still needed.

Comparison of automated and manual follicle monitoring in an unrestricted population of 100 women undergoing controlled ovarian stimulation for IVF

BACKGROUND Ovarian response to gonadotrophin stimulation is monitored with serial ultrasound (US) examinations. Sonography-based Automated Volume Count (SonoAVC) is a relatively new three-dimensional (3D) US technology, which automatically generates a set of measurements including the mean follicular diameter (MFD) and a volume-based diameter (d(V)) for each follicle in the ovaries. The present study aimed to assess the applicability and reproducibility of this automated follicle measurement method in an IVF programme. METHODS For this prospective method comparison study, 100 women undergoing US monitoring of a controlled ovarian stimulation cycle were recruited. Each follicle was manually measured by taking the mean of maximal diameters on three orthogonal planes with two-dimensional (2D) US. A 3D volume of each ovary was then captured. The ovarian volumes were later analysed using SonoAVC. The agreement between the two methods for the numbers of follicles and the size of the leading follicle was assessed with the Bland-Altman method. The reproducibility of SonoAVC measurements was assessed with the intraclass correlation coefficient (ICC). RESULTS Both SonoAVC-generated MFD and d(V)-based follicle counts, as well as the leading follicle diameter, had good agreement with conventional 2D US measurements. SonoAVC measurements had very good reproducibility, with ICC ≥0.8 for most evaluations. CONCLUSIONS Automated follicle monitoring with SonoAVC can replace or be used interchangeably with conventional 2D measurements. Automated follicle monitoring can save time, provide a method of quality control and create opportunities for developing HCG criteria based on follicular volume or for monitoring patients from a distance.

PCOS patients can benefit from in vitro maturation (IVM) of oocytes

OBJECTIVE Our aim was to compare treatment outcome following in vitro maturation (IVM) compared with IVF in patients with polycystic ovarian syndrome (PCOS). STUDY DESIGN Retrospective evaluation of treatment in women with PCOS who underwent IVM (108) and IVF (108). RESULTS We found a significant difference in outcome between IVM and IVF, with an increase in the number of mature oocytes derived (10.5 ± 6.5 vs. 15.3 ± 8.8, p<0.0001) and the cleavage rate (92.4 ± 13.0 vs. 95.2 ± 11.7, p=0.03) in IVM cycles. Due to the lower implantation rate (16.1% vs. 21.6%, p=0.07) we tend to transfer more embryos in the IVM group (3.4 ± 0.8 vs. 2.8 ± 1.0, p<0.0001), but the multiple pregnancy rate in that group was not higher. Importantly, the delivery rate was similar in both groups (26.8% vs. 25%). We also report a yearly change in the success rate of IVM during this period. CONCLUSIONS IVM treatment for PCOS patients may be a valid alternative treatment to IVF with the advantage of eliminating the risk of OHSS and reducing the cost of medication, whilst maintaining high clinical pregnancy rate.

Ovarian stimulation and intrauterine insemination in women aged 40 years or more

Fertility decreases with advancing age. This study retrospectively reviewed the results of ovarian stimulation and intrauterine insemination (IUI) in women 40 years old with diminished ovarian reserve or unexplained infertility who underwent treatment with ovarian stimulation/IUI with clomiphene citrate or gonadotrophin and compared them with the results of IVF and in-vitro maturation (IVM) treatments. The main outcome measures were pregnancy and live-birth rates. The profiles of the patients in ovarian stimulation, IVM and IVF groups were comparable. There were no clinical pregnancies in the clomiphene citrate and IVM groups. The clinical-pregnancy rates in the gonadotrophin and IVF groups were 2.6% and 16.9% and the live-birth rates were 2.6% and 13.7%, respectively. Compared with ovarian stimulation, IVF is most effective for women aged 40 years or more. Attempting success with ovarian stimulation or IVM will delay conception unnecessarily.

In vitro maturation of oocytes as a strategy for fertility preservation.

In vitro fertilization and embryo cryopreservation are regarded as the only established method for the preservation of fertility in female cancer patients. However, a possible delay in the treatment of cancer and exposure to supraphysiologic estrogen levels caused by ovarian stimulation raise concerns for patients and physicians. In vitro maturation avoids treatment delay or exposure to increased estradiol levels associated with in vitro fertilization. In vitro maturation combined with embryo or oocyte vitrification provides options that have been unavailable earlier, such as immature oocyte collection in the luteal phase, for some patients and improves the services provided by a fertility preservation program.