| Abstract |
TITLE
Comparison of anthropometric and hormonal parameters and the receptivity of the endometrium (implantation rates, biochemical and clinical pregnancy) IVF-OD between recipient oocytes with a history of endometriosis and recipient without endometriosis.
INTRODUCTION
Endometriosis is a benign gynecological disease of reproductive age and according to symptoms affecting quality of life of the woman (Simoens S et al., 2007; Simoens S et al., 2012). Although laparoscopy is the gold standard for diagnosis of endometriosis, the possibility can be diagnosed and assessed its impact on less invasive means such as the use of a biological indicator (biomarker), could be extremely high economic and social importance.
Although many mechanisms have been proposed to explain how endometriosis is associated with infertility, there is no important data on the effect of endometriosis on implantation of the fertilized oocyte and the uterus receptivity. Trying to understand if the endometrium, the oocyte, or both are affected by endometriosis was used the egg donation model.
Whilst it is accepted that endometriosis regresses when women nearing menopause, irreversible epigenetic changes of the endometrium in women with endometriosis (Cakmak H and Taylor HS, 2010b), as well as reactivation of endometriosis in women who have passed menopause, with or without hormonal
therapy, has been observed in several cases (Nisolle-Pochet M et al., 1988; Goumenou AG et al., 2003; Oxholm D et al., 2007).
AIM OF THE STUDY
The present study comparing anthropometric and hormonal factors aims to investigate whether endometriosis affects the receptivity of the endometrium in women with a history of endometriosis, in an egg donation program and shared eggs with women who had free history of endometriosis.
SUBJECTS AND METHODS
Women in the study were divided into 2 groups: the first group (I) included 210 women with a history of endometriosis, which were recipient oocytes. The second group (II) included 210 women without history of endometriosis who shared donor’s oocytes with women from group I. Also, during the study arose other four subgroups of women by variable menopause. The third group (III) consisted of 102 women with a history of endometriosis in menopause. The fourth (IV) group included 108 women with a history of endometriosis and no menopause. The fifth group (V) included 98 women with no history of endometriosis and menopause. The sixth group (VI) included 112 women with no history of endometriosis and no menopause.
The parameters identified are divided into three categories. A complete history recorded in the patient 's first visit by completing a prescribed form. The form included basic demographic data (age, weigh, smoking, history of obstetric deliveries and abortions, menarche, frequency and duration of menstruation) and ultrasound and laboratory findings (bloodcontrol, immunological control, time of blood coagulation, cultures) . B On the 3rd to 7th day of the cycle preceding IVF measured in blood, the following factors : FSH, LH, estradiol, CA-125, IL-6, VEGF, AMH. C. Documentation and all elements of effort ( number of eggs , mature eggs , number of 2PN, 2PN scoring, cleavage rate, embryo assessment) and the receptivity of the endometrium ( pregnancy rate , implantation rate, biochemical and clinical pregnancy , abortions and live births ) .
The age of the donor is a key factor in achieving pregnancy as it is known that a woman's age is inversely related to the quality of oocytes, all donors were under 32 years of proven fertility, having at least one child. The most common protocol used for ovarian stimulation of the donor was the long protocol, and sometimes the corresponding using GnRH antagonists.
The fertilization of the mature oocytes (stage of the second meiotic division) was made by the method of microinjection (ICSI). Embryos were evaluated on the morning of the second, third or fifth day of their culture and were selected the best ones (grade 1 and grade 2) for transfer to the recipient (maximum number of embryos 3), while supernumerary good quality were frozen and by the method of vitrification (Vanderzwalmen P et al., 2009). The embryotransfer held under ultrasound monitoring (Prapas Y et al., 1995). Pregnancy was confirmed 14 days after embryo transfe with finding of a positive pregnancy test. A clinical pregnancy was defined as coexistence amniotic sac and positive cardiac function between 8th and 10th week of pregnancy. As defined by the ongoing pregnancy in which normal sonographic findings in 22 weeks of pregnancy. The implantation rate was defined as the ratio of the number amniotic sacks positive cardiac function to the number of transferred embryos. Finally, recorded the outcome of in vitro fertilization (biochemical - clinical pregnancy, miscarriage and live birth rate ) .
RESULTS
The analysis of the results showed that women with a history of endometriosis (Group I, n = 210) compared with women with no history of endometriosis (Group II, n = 210), showed statistically significant differences respecting age (p <. 0001 * ) and the smoking (p <. 0001 *). There was no statistically significant difference in terms of menopause, births and abortions were preceded menarche, BMI, and previous IVF attempts.
Also, regarding the hormonal and biochemical parameters there was not statistically significant difference in terms of the LH (mIU / ml) and AMH (pmol / ml). Differences were seen in all other measurements, specifically, it was significantly higher values of FSH (mIU / ml) for the women in Group II compared with those of the group I (p = 0.0067 *). In that regard however, the E2 (p <0001 *), CA125 (p = 0.0000 *), IL6 (p = 0.0000 *) and VEGF (p = 0.0000 *) values were higher for Group I compared to Group II.
Regarding laboratory data we observed that there was no statistically significant difference in any of the factors recorded ( number of eggs , number of MII oocytes , number 2PN, 2PN scoring, cleavage rate, number of embryos for embryo transfer (ET ), score of embryos) . Also, were higher for Group II compared to Group I Bhcg (p = 0.0007 *), clinical pregnancy (p <0001 *) and implantation rate (p <0001 *) and live birth rate (p <0001 *). While the miscarriage rate was again higher for women in Group II compared with women in Group I (p = 0.0043), the rate of going pregnancy was statistically higher for Group II compared with Group I ( p = 0.0004 *).
A further analysis of the results of women with no history of endometriosis and menopause (Group III, n = 102) compared with women with a history of endometriosis and menopause (Group IV, n = 108) showed statistically significant differences respecting age (p <0.0087 *) and the previous births (p 0.0471 *). There was no statistically significant difference in smoking, abortions, menarche, BMI, duration of the cycle and previous IVF attempts.
No statistically significant differences in terms of the LH (mIU / ml), the CA125 (U / ml) and AMH (pmol / ml). Differences were seen in all other measurements, specifically significantly higher values of FSH (mIU / ml) for women of Group IV compared with those of the Group III (p = 0.0428 *) of IL6 (p <.0001 *) and VEGF (p <0.0000 * ) .
Regarding laboratory data observed that there was no statistically significant difference in any of the factors recorded ( number of eggs , number of MII oocytes , number 2PN , 2PN scoring, cleavage rate, ithmos embryos for embryo transfer (ET ), score embryos) . Regarding laboratory data, we observed that there was no statistically significant difference in Bhcg, clinical pregnancy, biochemical pregnancy, (implantation rate), miscarriage rate, the on going pregnancy to live birth rate between Group III and IV.
Women without a history of endometriosis and no menopause (Group V, n = 98) compared with women without a history of endometriosis and menopausal Group VI (n = 112) showed statistically significant differences respecting age (p<0001 *), previous miscarriages (p= 0.0111 *), BMI (p = 0.0028 *). There was no statistically significant difference in smoking, menarche and previous IVF attempts.
There was no statistically significant difference only for AMH (pmol / ml) among women of Groups V and VI. Differences were seen in all other measurements, specifically it was significantly higher values of FSH (mIU / ml) for women of Group VI in relation to those of the Group V (p <.0001 *) and LH (mIU / ml) (p = 0.0202 *) . Instead, it was significantly higher values for females of Group V in relation to those of the Group VI of E2 (pg / ml) (p <.0001 *), the CA125 (U / ml) (p <.0001* ) of IL6 (p = 0.0000 *) and VEGF (p = 0.0000 *).
Regarding laboratory data observed that there was no statistically significant difference in any of the factors recorded (number of eggs, number of MII oocytes, number 2PN, 2PN scoring, cleavage rate, number of embryos for embryo transfer (ET ), score embryos ) , the Bhcg, clinical pregnancy, biochemical pregnancy, the rate of abortion (miscarriage rate), the on going pregnancy and live birth rate between Group III and IV. Regarding the miscarriage rate (24 versus 9, p = 0.0028 *) and implantation rate, the prices are significantly higher for Group VI in relation to Group V.
CONCLUSIONS
From the assessment of the results of this study it appears that women with a history of endometriosis, have statistically lower rates of implantation, pregnancy and live births, compared with women who received oocytes from the same donor, which had no history of endometriosis. These differences though were lower in comparison to menopausal women, but remained statistically significant. Thus, questions arose about whether irreversible epigenetic changes before menopause associated with endometriosis or recurrent postmenopausal endometriosis affect the outcome of IVF. However, the severity of endometriosis did not affect these results and that's why the number of women who participated in the work was great, limiting the statistical error.
In conclusion, the receptivity of the endometrium affected by endometriosis, even when women have gone through menopause and has negative effects on implantation, pregnancy and live birth rate and therefore, it is important to carefully assess each recipient with a history of endometriosis.
From biochemical indices endometrial analyze the conclusion drawn was that only the IL-6 and VEGF changing with menopause, while no changes occur AMH and Ca-125. More specifically, in recipient oocytes without history of endometriosis, after menopause, the levels of both IL-6 and VEGF in reduced while women with a history of endometriosis who are going through menopause these levels increase. However, from our results it appears that the rates of implantation, pregnancy and live birth not affected by these indicators.
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