Prediction Of Ovarian Response To Gonadotrophin Stimulation In In-vitro Fertilization:

Mahmoud A. Gehad

Recruitment and development of multiple follicles in response to gonadotrophin stimulation are the key factors leading to successful treatment by IVF and ET or other assisted reproductive methods (Ng, 2000).Production of ovarian responses prior to stimulation is useful in counseling patients and may be helpful in tailoring the dosage of gonadotrophin to individual patients (Frattareli et al., 2003).But, how could we implement the knowledge we have on predictive factors in clinical practice?The problem is that standard patients treated with standard doses frequently do not exhibit standard response.The variability in the responses may be due to inherent biological mechanisms in relation to difference in the number of recruitable follicles, follicle sensitivity and pharmacodynamics on the other hand they may be due to factor or factors that may be predicted and treated or controlled. (Hendriks et al., 2005).This study compared the predictive value of age of women, bodymass index, infertility years, basal serum FSH concentration, basal serum LH concentration , basal FSH/LH ratio, basal serum E2 concentration, basal serum sept in hormone concentration, total ovarian volume and antral follicle count in relation to the number of oocytes obtained (as a 1ry outcome) and in relation to pregnancy rate (a secondy centcome) in 50 infertile women undergoing IVF treatment.Smokers and those with only one ovary or having previous operation on ovaries are known to impair ovarian on ovaries are known to impair ovarian response and were excluded, also patients with PCo and ovarian cysts that interfere with ovarian volume were excluded from the study.In order to avoid other confounding variables, the study group consisted of women undergoing their first IVF cycle and receiving the same standard long protocol.As regarding the number of oocytes retrieved:This study confirms and extends earlier studies by showing that the following single factors could predict the number of retrieved oocytes: Age, BMI, FSH, Leptin hormone, ovarian volume and antral follicle count with a strong correlation (p < 0.01), a higher number of antral follicles and ovarian volume resulted in more oocytes obtained with lower dose of gonadotrophin ampoules, whearas higher basal FSH concentration, higher BMI, higher leptin concentration and increasing age will impair ovarian response and decrease the number of oocytes obtained after stimulation. However, using stepwise multible regression analysis using the number of oocytes obtained as the dependent variable with constant included in the equation revealed that AFC is the single most important predictor of oocyte count (p < 0.001) followed by FSH (p < 0.01) & ovarian volume (p < 0.05) table ( ).The following formula could predict nearly the number of oocytes from the following equation oocyte count = 1.373 + 0.702 (FAC)- 0.391 (FSH) + 0.386 (ovarian volume) a logistic regression analysis regarding prediction of poor ovarian response revealed that FSH & AFC were the only variable chocen by the model analysis to predict ovarian response.These findings coincide with the results of Hendriks et al., (2005) who stated that FAC might be considered the test of first choice in the assessment of ovarian reserve prior to IVF.Syrop et al., (1999) concluded that the introduction of AFC & ovarian volume measurement refined and improved the prediction of ovarian response also (Tomas et al., 1997; Lass et al., 1997; Change et al., 1998 and Hansen et al, 2003). Stated that the number of antral follicles was correlated more strongly with the number of oocytes retrieved and AFC is better than ovarian volume, age or other biochemical markers.The data of the present study confirms the findings of (Bansci et al., 2002).that the number of antral follicles decreases proportionately with patients age and with increasing FSH level.The explanation of this correlation is believed to be that antral follicles are the main source of inhibin secretion, which decreases FSH release from the anterior pituitary gland a decrease of antral follicle cohort increases serum FSH level (Bansci et al., 2002).Also, Popovic-Todorovic et al., 2003 and Goswany et al., 1998) stated that AFC was obetter predictor and it may be used as the first method for predicting the ovarian response to gonadotrophins. However ovarian volumetry is accurate and easily preformed in most women with small intra-and inter observer variations so in the situation where the quality of ultrasound image may be impaired by any factor, the estimation of AFC may prove to be a difficult task especially the very small antral follicles with 2-3mm in diameter. Ovarian volume could thus be considered as a safety variable.Kable-Ambe et al., (2001) and Syrop et al., (1995) concluded total ovarian volume to be a predictor distinct from age for predicting the ovarian response.Tomas et al., (1997) and Syrop et al., (1999) found that total ovarian volume appeared to be correlated with the number of oocytes and women with decreased ovarian volume required more gonado trophins and obtained fewer oocytes and greater cancellation rate. Ovarian volume provides information to the clinicians and patients before starting the trial: this is an easy, inexpensive with minimal invasiveness.Sharara et al., (1999); Chuang et al., (2003) and Toner et al., (2003) stated that fertility is remarkably reduced with increasing age of women. The decreased fertility is apparently due to decreasing number of primordial follicles from > 250000 at menarche to only a few humreds or thovsands at the end of the reproductive life.Chuang et al., (2003) concluded that both age and FSH contributed to the prediction of the quantitative ovarian reserve as reflected by the number of oocytes collected.Creus et al., (2000), Onagawa et al., (2004) and Iwase et al., (2005) found a negative correlation between serum basal FSH and oocytes number and concluded that FSH is better than age in predicting the quantity (but not the quality of oocytes) Van Rooij et al (2003) illustrated the important biological distinction between ovarian reserve that is a better predictor of egg production capacity and the egg quality and concluded that age = quality & FSH = quantity.In the present study oocyte quality was significantly correlated only with age & leptin hormone (-ve correlation) p value (< 0.01). However there were no significant difference between poor and good responder as regarding oocyte quality & fertilization rate. Also cancellation rate was significantly these finding coincide with the dependent on FSH, AFC and leptirhomone log.Crues et al., (2000), Chuang et al., (2003) and Iwase et al., (2005) who concluded that FSH was a better predictor of cycle cancellation & poor response whearas age was a better predictor of oocyte quality.As regarding pregnancy ratesWhen comparing pregnancy success and pregnancy failure, age and basal leptin hormone level were the only variables independently associated with pregnancy rate (p value < 0.01) table ( ).Logistic regression analysis for age, patient characteristics basal hormone concentration & U/S features as predictors of pregnancy failure revealed that age was the variable independently associated with pregnancy rate (p < 0.01) followed by basal leptin hormone level (p < 0.05) i.e. increasing age & high basal leptin level were associated with a higher probability of pregnancy failure.This coincide with the findings of Change et al., (2003) and Creus et al., (2000) concluded that increasing age but not FSH was significantly associated with reduced pregnancy rate.Logistic regretion analysis revealed that age was an independent predictor of pregnancy rate.Gorgios et al., (2005) concluded that elevated leptin concentration were associated with reduced ovarian response, oocyte quality and pregnancy success leptin may serve as markers of IVF outcome.Gabriec & Szymanski (2002) and Curbuz et al., (2005) also concluded that leptin hormone has an advantageous effect on oocyte, zygote development.Brannian et al., (2001) documented a strong –ve relationship between leptin hormone and pregnancy success.This could be explained as leptin in a physiologicalregulator of oocyte developmental competence acting indirectly via the follicle and directly via actions on the oocyte it is therefore quite possible that elevated leptin concentrations might have a negative impact on oocyte developmental competence in IVF cycles. impaired uterine respectively in also possible (Alfer et al., 2000).Butzow et al., (1999) showed that a large relative increase in leptin was associated with diminished ovarian response to gonadotrophin. Furthermore, leptin may influence outcomes from IVF, patients who become pregnant from IFV had lomer mean concentrations of leptin than patients who did not become pregnant (Mantazoros et a., 2000).This may be explained by the negative correlation between leptin concentration and intra follicular oxygen tension which negatively impact oocyte maturation (Barroso et al., 1999).In spite of the high predictive effect of AFC & FSH on ovarian reserve the failed to find an effect of these variables on pregnancy rates. Obviously, the occurance of pregnancy is influenced by many more factors than ovarian reserve (Abdalla and Thum, 2004).ConclusionThe results of this study indicate that the number of antral follicles is the best currently available basal number of antral follicles is the best currently available basal marker of ovarian reserve in terms of predicting poor response in IVF. In itself, the performance of the antral follicle count is only fair. Because the availability of transvaginal ultrasonography is a prerequisite for IVF, counting the number of antral follicles and ovarian volume and could be considered as a standard ovarian reserve screening test before IVF is applied. If maximum accuracy in counseling is warranted, endocrine testing, especially of FSH and laptin hormone should not be abandoned, as it will provide additional predictive information in addition to the antral follicle count.Although there is a reduction in both PR and LBR associated with higher levels of basal FSH and low AFC it is clear that in cycling women, high basal FSH is not a contraindication to IVF treatment, and a respectable PR and LBR can be achieved especially in young women. The reduction in PR and LBR is due to reduced reserve rather than poor oocyte quality. Clinics refusing to treat cycling women with elevated basal FSH levels may be denying these women a reasonable, albeit low, chance of achieving a birth with their own genetic material. Clinicians should use basal FSH levels as a guide to advise patients about their chances of achieving a live birth, not to exclude patients with a predicated lower success rate from a treatment programme.