GnRH agonist early follicular challenge test as a predictor of ovarian response in antagonist cycles for fertility preservation.

The aim of our study was to evaluate if the response to follicular GnRH agonist (GnRHa) trigger be used to predict intracycle ovarian response in GnRH antagonist cycles among women undergoing fertility preservation IVF. We conducted a prospective study of 146 GnRH antagonist oocyte pickup (OPU) cycles to evaluate GnRHa stimulation test (GAST). On day 2 of the cycle, basal E2 were measured, followed by injection of 0.2 mg GnRHa as part of the initial ovarian stimulation. 12 h later blood sampling was repeated (GAST E3). E2 response was used as test parameter. The major outcome was the number of mature cryopreserved oocytes. We found a linear correlation between both GAST E3 level and GAST E3/E2 ratio and number of M2 oocytes. ROC curve analysis of GAST E3, GAST E3/E2 ratio, AFC and day 3 FSH for > 15 M2 and < 5 M2 oocytes was calculated. For GAST E3 levels obtaining < 5 M2 oocytes, an AUC value of 0.79 was found. For GAST E3 levels obtaining > 15 M2 oocytes, AUC value of 0.8. Patients with GAST E3 ≤ 384 pmol/l has 58.6% risk to obtain < 5 oocytes. Patients younger than 35 with GAST E3 > 708 pmol/l have 66% chance for freezing > 15 oocytes. The response to single GnRHa administration during GnRH antagonist cycle can be used as biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict the response of the specific cycle, and can potentially be used to adjust the treatment dose.Trial registration number: 0304-20-ASF.

Follicular challenge test to predict suboptimal response to gonadotropin releasing hormone agonist trigger in elective oocyte cryopreservation cycles.

This prospective study aimed to test the ability of follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger, assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program. The study included 91 women that underwent non-medical fertility preservation. On day two to menstrual cycle, blood tests were drawn (basal Estradiol, basal FSH, basal LH, Progesterone) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist (FACT) and arrive for repeated blood workup 10-12 h later in the next morning, followed by a flexible antagonist protocol. LH levels on the morning after ovulation trigger were compared to FACT LH levels. The results demonstrated that LH levels following agonist ovulation trigger below 15IU/L occurred in 1.09% of cycles and were predicted by FACT, r = 0.57, p < 0.001. ROC analysis demonstrated that FACT LH > 42.70 IU/L would predict LH post trigger of more than 30 IU/L with 75% sensitivity and 70% specificity, AUC = 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p < 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the number of frozen oocytes was progesterone levels post agonist trigger (r = 0.746, p < 0.001). We concluded that suboptimal response to agonist trigger, as assessed by post trigger LH levels was a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate LH levels elevation after agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders.

Endometrial compaction is associated with increased clinical and ongoing pregnancy rates in unstimulated natural cycle frozen embryo transfers: a prospective cohort study.

PURPOSE: To investigate the association between endometrial compaction and pregnancy rates in unstimulated natural cycle frozen embryo transfers. DESIGN: A single-center prospective cohort study. Endometrial thickness by transvaginal ultrasound and blood progesterone levels on the day of ovulation and the day of embryo transfer were evaluated in patients undergoing natural cycle frozen embryo transfer. Compaction was defined as > 5% decrease in endometrial thickness between ovulation day and day of transfer. Clinical and ongoing pregnancy rates in cycles with and without compaction were compared. RESULTS: Seventy-one women were included, of which 44% had endometrial compaction, with similar rates when subdividing the patients by day of transfer (day 3 or day 5). Clinical and ongoing pregnancy rates were higher in the compaction group compared to the non-compaction group (0.58 vs. 0.16, P < 0.001; 0.52 vs. 0.13, P < 0.001 respectively). Subdividing by degree of compaction > 10% and > 15% revealed similar pregnancy rates as > 5%, with no added benefit to higher degrees of compaction. CONCLUSIONS: About half the patients in our study undergoing unstimulated natural cycle frozen embryo transfer experienced compaction of the endometrium, occurring as early as day 3 post-ovulation. This was significantly correlated with increased clinical and ongoing pregnancy rates.

A previous caesarean section is not a risk factor for tubal abnormalities in the infertile population.

In this retrospective cohort study of 1716 cases of women undergoing infertility treatment between the years 1999-2012, we aimed to identify whether parturients with a previous surgical history are at a higher risk for tubal abnormalities as determined by hysterosalpingography (HSG) in this infertile population. Amongst the study population, tubal obstruction was identified on HSG in 15.8% of patients with no past history of an abdominal surgery and 16.3% of patients with a previous caesarean section (CS) delivery. These rates were significantly lower than those for women with a previous gynaecological surgery (34.7%) or abdominal surgery (27%) (p < .001 for all comparisons). Our results suggest that past history of CS poses no additional risk for tubal abnormality within the infertile population, whereas a history of other abdominal or gynaecological surgical procedures doubles this risk. Impact Statement What is already known on this subject? While numerous risk factors for tubal factor infertility have been established, to date, the relation between previous abdominal surgeries and the risk for tubal factor infertility remains inconclusive. What the results of this study add? In this study, we aimed to evaluate the correlation between previous CS history and the risk for having tubal factor infertility. Our results demonstrated that previous caesarean section delivery does not increase the risk for tubal factor infertility in the infertile population, whereas history of other abdominal or gynaecological surgical procedures doubles this risk. What the implications are of these findings for clinical practice and/or further research? Further research is needed for further evaluation of this association and its clinical implications.

Endometrial nerve fibre density in patients undergoing IVF: a pilot study.

The presence of nerve fibres in the functional layer of the endometrium has been strongly associated with endometriosis. Presence of nerve fibres in the endometrium of women undergoing IVF has not been previously assessed. This prospective pilot study assessed the presence of nerve fibres in endometrium of women undergoing IVF due to various causes and examined the correlation between the presence of nerve fibres and IVF success. A total of 32 IVF patients underwent endometrial biopsy during days 21-23 of the menstrual cycle. Nerve fibres were identified by immunohistochemical staining. Correlations between the presence and density of nerve fibres and aetiology of infertility and IVF success were measured. Nerve fibres were identified in the endometrium of 10/31 (32.3%) women with a satisfactory biopsy. Presence of nerve fibres was not correlated with cause of infertility. Clinical pregnancy was achieved in 12/32 (37.5%) patients, without correlation to presence of nerve fibres in the endometrium. Nerve fibres were identified in a substantial percentage of women undergoing IVF, possibly reflecting underdiagnosis of endometriosis in this population. The presence of nerve fibres does not appear to interfere with implantation. The significance of nerve fibres in the endometrium of IVF patients warrants further research. The presence of nerve fibres in the functional layer of the endometrium has been strongly associated with endometriosis. The presence of nerve fibres in the endometrium of women undergoing IVF has not been previously assessed. Our aim was to assess the presence of nerve fibres in endometrium of women with various causes of infertility undergoing IVF and to examine the association between the presence of nerve fibres in the endometrium and IVF success. In a prospective study, 32 IVF patients underwent endometrial biopsy during days 21-23 of the menstrual cycle. Nerve fibres were identified by immunohistochemical staining. Associations between the presence and density of nerve fibres and the aetiology of infertility and IVF success were measured. Nerve fibres were identified in the endometrium of 10/31 (32.3%) women with a satisfactory biopsy. No association was found between the presence of nerve fibres and the cause of infertility. Clinical pregnancy was achieved in 12/32 (37.5%) patients, without association with the presence of nerve fibres in the endometrium. Nerve fibres can be identified in a substantial percentage of women undergoing IVF, possibly reflecting underdiagnosis of endometriosis in this population. Their presence does not interfere with embryo implantation. The significance of nerve fibres in the endometrium of IVF patients warrants further research.

Two-dimensional and three-dimensional Doppler assessment of fetal growth restriction with different severity and onset.

OBJECTIVES: To investigate the role of three-dimensional (3D) power Doppler ultrasonography in the assessment of fetal growth-restriction (FGR) with various degrees of severity and onset, and compare the results with the analysis of two-dimensional (2D) Doppler. STUDY DESIGN: Vascular indices extracted from 3D Doppler measurements of the placenta were compared with indices of flow-velocity waveforms extracted from 2D Doppler measurements of the major sites of the fetal circulation between FGR (study group) and uncomplicated pregnancies (control group) from 25 to 38 weeks' gestation. RESULTS: Three-dimensional indices were significantly lower in pregnancies complicated by FGR compared with uncomplicated pregnancies. When measured in placental periphery, vascularization index was 9.4 ± 9.6 in FGR pregnancies compared with 16 ± 14.7, P = 0.04. Flow index was 33.9 ± 6.9 compared with 38.7 ± 4.9, P = 0.03 and the vascularization-flow index was 3.8 ± 4.3 compared with 6.5 ± 6, respectively, P = 0.03. Among the conventional 2D indices, umbilical artery and middle cerebral artery pulsatility indices were not significantly different between the FGR and control groups. Higher rate of maternal or fetal compartment vascular lesions were detected in the FGR group. CONCLUSIONS: Three-dimensional Doppler was found to be more strongly associated with placental vascular compromise than conventional 2D Doppler, regardless of severity and onset of fetal growth restriction.