الفهرس 
FACTORS AFFECTING THE OUTCOME OF IN INVITRO INTRACYTOPLASMICOnly 14 pages are availabe for public view
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Abstract
C
ontrolled ovarian hyper-stimulation (COH) causes excessive follicular development and supra-physiological serum concentrations of estradiol (E2) in the follicular phase and progesterone (P4) in the luteal phase. The experience with human ART had revealed many relationships between successful conception and the concentration of steroid hormones and thus provides evidence to predict treatment outcomes.
Since successful implantation depends on the quality of the embryo and a receptive endometrium, it was found that high serum progesterone levels have no adverse effect on the embryo itself as determined by pregnancy outcome following embryo transfer using donated eggs, but the main adverse effect of a rise of progesterone during controlled ovarian hyperstimulation seems to be on the endometrium.
In the literature, the relationship between progesterone elevation in the day of hCG and pregnancy rate has been analyzed with wide range thresholds and no conclusive cut off value was reached. Also since the rise in progesterone is explained by the increase in ”granulosa cell mass” a group of investigators proposed to use a ratio between progesterone /estradiol (P/E2) on the day of hCG with cut-off value > 1, but they also reported that P/E2 ratio cannot be used as a reliable predictor for pregnancy rate.
So the day of oocyte retrieval is a provocative time point. Willman & Hinckley were the first to investigate the impact of serum progesterone level on the day of oocyte retrieval in both agonist and antagonist protocol and reported that serum progesterone level on the day of oocyte retrieval does not influence pregnancy outcome. However in 2008, Niu and his colleagues reported the same observation but they found a correlation between serum progesterone level and quantity of viable embryos in patient undergoing intracytoplasmic sperm injection using GnRH- agonist both long and short protocol.
The same observation was stated 2 years latter that high serum progesterone levels were significantly correlated with higher number of follicles >15mm, oocytes retrieved and embryos transferred.
Ochalski and his colleagues concluded that elevated progesterone level on the day of oocyte retrieval with cutoff value (> 10 ng/ml) negatively impacts intracytoplasmic sperm injection outcome in short antagonist protocol.
Later, a prospective cohort study reported that implantation rate (positive hCG 14 days after embryo transfer) and pregnancy rate were significantly higher when the progesterone level was < 12 ng/mL on the day of oocyte retrieval in short antagonist protocol.
Different strategies have been developed to evaluate endometrial receptivity, such as the histological dating of an endometrial biopsy, endometrial cytokines in uterine flushing, the genomics study of a timed endometrial biopsy, 3D power or color Doppler. All this strategies failed to be reliable, but the non invasive ultrasound examination of the endometrium was superior such as endometrial thickness and pattern.
Endometrial thickness has been utilized as an indirect indicator for endometrial receptivity and is measured in the mid-sagittal plane during transvaginal ultrasound, which is considered as both a-traumatic and simple. The effect of endometrial thickness on pregnancy rates in patients undergoing intracytoplasmic sperm injection has been evaluated by many authors, with controversial results. Some authors demonstrated a higher pregnancy rate at certain endometrial thickness, while others did not show a significant correlation between endometrial thickness and pregnancy rate. Other authors reported a threshold of <7mm and/or >14mm with a significant reduction in implantation rate and pregnancy rate.
Regarding endometrial pattern or morphology, a non triple-line endometrial pattern seems to be associated with a less favorable outcome, while a triple-line endometrial pattern appear to be associated with better pregnancy rate.
This prospective observational study was carried out between the period from November 2012 to August 2014 on 116 infertile women, each woman in the study was subjected to obtaining informed consent, full history taking, complete physical examination, baseline transvaginal ultrasound, baseline hormonal profile.
Then they were subjected to controlled ovarian hyperstimulation by using the long GnRH-agonist protocol after fulfilling the following inclusion criteria 1) Age >19 years and < 40 years, 2) BMI > 18.5kg/m2 and < 35kg/m2, 3) No evidence of uterine pathology. Folliculometry was done till the largest follicle diameter reach ≥ 18mm then trigger was given and planned oocyte retrieval was done 34-36 hour after.
On the day of oocyte retrieval serum progesterone, endometrial thickness and endometrial pattern were assessed. Assessment of fertilization was done followed by grading of the embryo using zygote then cleavage stage then blastocyst grading systems in timely manner. Finally embryo transfer was done on day 3 or day 5 for good quality embryos, the outcome in the form of clinical pregnancy was checked.
The results showed that average serum progesterone level was 6.5±4.1ng/ml, mean endometrial thickness was 9.9± 2.1 mm, and triple-line endometrial pattern was found in 78.4%. The clinical pregnancy per ovum pickup was 65(56.0%), while the clinical pregnancy per embryo transfer was 65(57.0%).
Comparison between patients with negative or positive clinical pregnancy was done and there was no significant difference between both groups regarding serum progesterone level or endometrial thickness, but there was a statistically significant difference between patients with negative or positive clinical pregnancy as regard to triple-line endometrium.
ROC curve analysis showed that neither serum progesterone nor endometrial thickness was predictive for clinical pregnancy with AUC 0.512 & AUC 0.523 respectively. While endometrial pattern was predictive for clinical pregnancy with AUC 0.710, sensitivity 96.9% specificity 45.1% PPV 69.2 %, NPV 92.0%.
Although it was found that there was no significant correlation between patients with negative or positive clinical pregnancy regarding serum progesterone level on the day of oocyte retrieval. However, there was a statistically significant relation with moderate correlation between serum progesterone and number of retrieved oocytes, number of M2 oocytes, number of fertilized oocytes. Multivariable regression analysis showed also that serum progesterone level was independent predictor to the theses variables.
To assess the influence of other variables that may contribute for the clinical pregnancy rate a multivariable binary logistic regression analysis was done and showed that serum progesterone, endometrial thickness are not independent predictors for the clinical pregnancy rate, while age and triple-line endometrium was the only independent predictors of the clinical pregnancy rate.