Follicular Fluid Interleukin-6 in Patients with Unexpected Poor Responseafter Controlled Ovarian Hyperstimulation in In-Vitro Fertilization/Intra-Cytoplasmic Sperm Injection Cycle
Tarek Hesham El-Sayed Mohammed;
Abstract
The follicular response to controlled ovarian hyperstimulation (COH) is essential to the performance of assisted reproduction by in-vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI). The possibility to fertilize more than one oocyte clearly improves the chances for a successful treatment compared with the limited prognosis after a natural unstimulated cycle (Stoop et al., 2012).
Failure to respond adequately to standard protocols and to recruit adequate follicles is called “poor ovarian response”. This results in decreased oocyte production, cycle cancellation and, overall it is associated with a significantly diminished probability of pregnancy (Venetis et al., 2010).
In this study poor ovarian response (POR) will be determined as having one of the following criteria in the current cycle:
• Low serum Estradiol (E2) levels (500 pg/ml or less) measured on the day of Human Chorionic Gonadotropin (HCG) administration (Davar et al., 2011).
Or
• Less than four oocytes retrieved on the day of ovum pick up (Ozmen et al., 2009).
One of suggested mechanisms for poor ovarian response is immunological abnormalities including cytokines disturbances(Sarapik et al., 2010).
Interleukin 6 (IL-6) expression is described within the human granulosa cells of the Graafian follicle, in the human corpus luteum and ovarian theca cells, the endometrium and in the pre-implantation embryo. Measurements of follicular fluid (FF) levels of IL-6 in women undergoing in vitro fertilization (IVF) have been shown previously to be associated with etiology of infertility, stimulation protocol, fertilization rates and pregnancy outcome (Richards et al., 2008).
In our study, a total of 1248 women, planned for IVF-ET, were recruited in the study; of them 140 women were poor responders. This group of women were included as group I (Poor Responders Group). A sample of 140 women of the remaining good responders were selected to match the cases of group I regarding the age and BMI, and were included as group II (Good Responders Group). Frequency matching method was applied to select women of group II. High responders were not included in the latter group. Both groups were exposed to long protocol COH then follicular fluid is aspirated, collected and assayed for IL-6 by commercially available ELISA kit.
The aim of this study was to evaluate the relation and impact of the follicular fluid IL-6 level in relation to ovarian response to controlled hyperstimulation during an IVF cycle.
The secondary outcomes obtained from it were number of retrieved oocytes, the total dose of gonadotropins used during the controlled hyperstimulation and the positive pregnancy outcomes during those cycles.
In our thesis, we found that mean follicular fluid IL-6 concentration was significantly higher in poor responder women when compared to good responder group. Mean follicular fluid IL-6 in poor responder women was 84.95 pg/mL ± 56.47 while in good responder women was 14.65 pg/mL ± 5.01 with p value <0.001.
Also in our study, mean follicular fluid IL-6 concentration was significantly lower in women who had positive clinical pregnancy (CP) when compared to womenwho did not get pregnant; 21.6 pg/mL ± 16.81 and 61.48 pg/mL ± 58.65 respectively with a p value <0.001.
ROC analysis of the data of our study was done to estimate a cut-off value for follicular fluid IL-6 concentration for predicting the outcome of ICSI-ET, a percentage of M2 oocytes ≥ 50% and a fertilization rate ≥ 50%. A follicular fluid IL-6 concentration 32 pg/ml was significantly associated with successful clinical pregnancy at a sensitivity of 85.4% and a specificity of 55.6% , with at least 50% M2 oocytes at a sensitivity of 62.6% and a specificity of 58.4% and at least 50% fertilization rate at a sensitivity of 63% and a specificity of 61.1%.
There was a significant positive correlation between follicular fluid IL-6 concentration and each of total gonadotropin dose and number of stimulation days. There was a significant negative correlation between follicular fluid IL-6 concentration and each of number of retrieved oocytes, percentage of mature (M II) oocytes, number of fertilized oocytes and number of fertilization rate.
Failure to respond adequately to standard protocols and to recruit adequate follicles is called “poor ovarian response”. This results in decreased oocyte production, cycle cancellation and, overall it is associated with a significantly diminished probability of pregnancy (Venetis et al., 2010).
In this study poor ovarian response (POR) will be determined as having one of the following criteria in the current cycle:
• Low serum Estradiol (E2) levels (500 pg/ml or less) measured on the day of Human Chorionic Gonadotropin (HCG) administration (Davar et al., 2011).
Or
• Less than four oocytes retrieved on the day of ovum pick up (Ozmen et al., 2009).
One of suggested mechanisms for poor ovarian response is immunological abnormalities including cytokines disturbances(Sarapik et al., 2010).
Interleukin 6 (IL-6) expression is described within the human granulosa cells of the Graafian follicle, in the human corpus luteum and ovarian theca cells, the endometrium and in the pre-implantation embryo. Measurements of follicular fluid (FF) levels of IL-6 in women undergoing in vitro fertilization (IVF) have been shown previously to be associated with etiology of infertility, stimulation protocol, fertilization rates and pregnancy outcome (Richards et al., 2008).
In our study, a total of 1248 women, planned for IVF-ET, were recruited in the study; of them 140 women were poor responders. This group of women were included as group I (Poor Responders Group). A sample of 140 women of the remaining good responders were selected to match the cases of group I regarding the age and BMI, and were included as group II (Good Responders Group). Frequency matching method was applied to select women of group II. High responders were not included in the latter group. Both groups were exposed to long protocol COH then follicular fluid is aspirated, collected and assayed for IL-6 by commercially available ELISA kit.
The aim of this study was to evaluate the relation and impact of the follicular fluid IL-6 level in relation to ovarian response to controlled hyperstimulation during an IVF cycle.
The secondary outcomes obtained from it were number of retrieved oocytes, the total dose of gonadotropins used during the controlled hyperstimulation and the positive pregnancy outcomes during those cycles.
In our thesis, we found that mean follicular fluid IL-6 concentration was significantly higher in poor responder women when compared to good responder group. Mean follicular fluid IL-6 in poor responder women was 84.95 pg/mL ± 56.47 while in good responder women was 14.65 pg/mL ± 5.01 with p value <0.001.
Also in our study, mean follicular fluid IL-6 concentration was significantly lower in women who had positive clinical pregnancy (CP) when compared to womenwho did not get pregnant; 21.6 pg/mL ± 16.81 and 61.48 pg/mL ± 58.65 respectively with a p value <0.001.
ROC analysis of the data of our study was done to estimate a cut-off value for follicular fluid IL-6 concentration for predicting the outcome of ICSI-ET, a percentage of M2 oocytes ≥ 50% and a fertilization rate ≥ 50%. A follicular fluid IL-6 concentration 32 pg/ml was significantly associated with successful clinical pregnancy at a sensitivity of 85.4% and a specificity of 55.6% , with at least 50% M2 oocytes at a sensitivity of 62.6% and a specificity of 58.4% and at least 50% fertilization rate at a sensitivity of 63% and a specificity of 61.1%.
There was a significant positive correlation between follicular fluid IL-6 concentration and each of total gonadotropin dose and number of stimulation days. There was a significant negative correlation between follicular fluid IL-6 concentration and each of number of retrieved oocytes, percentage of mature (M II) oocytes, number of fertilized oocytes and number of fertilization rate.
Other data
| Title | Follicular Fluid Interleukin-6 in Patients with Unexpected Poor Responseafter Controlled Ovarian Hyperstimulation in In-Vitro Fertilization/Intra-Cytoplasmic Sperm Injection Cycle | Other Titles | مستوياتالإنترليوكين-6 فى السائل الجريبى فى حالات ضعف الإستجابة الغير متوقع للتنشيط الفائق للتبويض فى التلقيح الصناعى/الحقن المجهرى | Authors | Tarek Hesham El-Sayed Mohammed | Issue Date | 2015 |
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