Ovulation of normal female is a complex process involving many organs. The Three major organs that regulate human reproduction are the hypothalamus, the pituitary and the ovary. The hypothalamus pulsatile generator of reproduction, produce and secrete GnRH, which by reaching pituitary, evoke the release of FSH and LH. In response to gonadotrophins stimulation, the ovaries initiate a dynamic process of steroid genesis, which results in the formation of mature ovum ready to be fertilized. Any defect in this group of complex processes results in infertility, which affects up to one in seven couples nowadays. Proportion of these couples may be able to ultimately conceive, but for considerable proportion conception is unlikely without some form of medical intervention. IVF-ET and, more recently, ICSI are now commonly used treatment for infertility.
Currently, most ICSI cycles are carried out under an ovarian stimulation with the goal of achieving multiple follicles to increase the fertilization rate, more embryos for transfer and cryopreservation and increase the pregnancy rate.
The evaluation of ovarian reserve prior to initiation of ovarian stimulation is an important aspect of the infertility work-up of a woman requiring assisted reproductive techniques.
Age, AMH, day 3 FSH, inhibin B, antral follicle count, ovarian volume and several dynamic tests have been demonstrated to be correlated with ovarian response in ART.
Anti-Mullerian hormone is a member of the transforming growth factor-b superfamily. AMH is produced by granulosa cells from pre-antral and antral follicles.
Serum AMH levels have an excellent correlation with the number of antral follicles as determined by vaginal ultrasound.
Ovarian hyper-response is the opposite end of the spectrum of ovarian reserve and might lead to a potentially life threatening condition, the OHSS.
OHSS refers to an exaggerated ovarian response to gonadotrophin treatment. The syndrome has a broad spectrum of clinical manifestations, from mild illness needing only careful observation to sever illness requiring hospitalization and intensive care, being a potentially life-threatening condition.
Mild and moderate forms of OHSS may occur in 15–20% of all ovarian stimulation cycles, however, the severe form of the syndrome has been reported as frequently as1–3% .
Several primary and secondary risk factors for OHSS have been identified . However, their sensitivity and specificity for predicting hyper-response/OHSS is variable.
The key to preventing OHSS is the recognition of risk factors for OHSS leading to an individualization of gonadotrophin starting dose which should be the minimum dose necessary to achieve the therapeutical goal or to achieve OHSS free clinic by use of GnRH antagonist.GnRH agonist for trigger of ovulation and cryopreservation of the embryos.
However, the accurate prediction of OHSS in an individual IVF cycle remains a difficult task. Indeed, PCOS (the main risk factor used in the prediction of OHSS) is present only in 20% of women undergoing COH and in, 20% of patients developing symptoms of impending OHSS .
The recognition of a dose–response relationship between AMH and ovarian response to FSH leads to the hypothesis that hyper response to ovulation induction might result from high AMH. In this context high basal AMH may be associated with an increased risk of developing OHSS.
This prospective study was designed to determine the possible relationship between serum anti-Müllerian Hormone concentrations and antal follicle count as a predictor of ovarian hyper stimulation and reproductive outcomes in women going to have an ICSI cycles.
Among two hundred and fourty infertile women undergoing assisted fertilization attending the ART unit in Benha university hospital and other private centers subjects were selected from (June 2014 to December 2015).
The study design was approved from medical ethical committee. Diagnosis of the couples will be confirmed by basic infertility work up and investigations. Patient included in this study had written informed consent for IVF-ICSI the age less than 35 years old, with no evidence of endocrine disorders.
The exclusion criteria were: Patients having uterine anomalies such as submucous fibroid, intrauterine synechiae and endometrial polyps. Basal day 2 U/S show ovarian cyst. Patient having previous ovarian surgery or single ovary or patient with poor ovarian response.
Basal hormonal profile including serum AMH determined and basal day 2-3 small AFC (2-6mm) measured via trans vaginal ultrasound before the index cycle.
Then, each eligible patient was received standard long protocol. Gonadotrophins stimulation via 150-300 IU of daily HMG stimulation will be initiated on the third day of subsequent withdrawal bleeding.
o Further HMG doses will be determined according to the standard criterion of follicular maturation, assessed by ultrasound and serum estradiol measurements.
o All patients were monitored by serum E2 and trans-vaginal ultrasound. Starting from the 6th day of stimulation, hCG 10,000IU was given IM for triggering of ovulation when at least 3 follicles reached 18-20mm. retrieval was performed 35 hours after the hCG by transvaginal ultrasound-guided needle aspiration under general anesthesia. ICSI was performed according to the protocol of Van Steirteghem. Luteal phase support was given to the patients in the form of daily 100mg progesterone in oil intramuscular injection for 14 days, and then beta hCG titer was performed for detection of pregnancy which confirmed by ultrasound examination at 5-6 weeks gestation by visualization of gestational sac.
Eighteen out of 240 IVF ICSI cycles were complicated by OHSS 16 moderate and 2 severe OHSS.
The patient then divided into 2 groups, group I (non OHSS) and group II (OHSS)
Basal AMH levels, small AFC, the E2 level on the day of hCG administration, and the number of retrieved oocytes, were significantly higher in OHSS. basal FSH and total dose of gonadotropins were significantly lower in OHSS, Age and BMI show no significant difference between both groups.
We found that AMH ≥ 3.2 ng/ml can predict moderate and sever OHSS with sensitivity 88.9% specificity 86.5% PPV 57.1 % NPV 98.9% accuracy 86.7% and that of small AFC (2- 6mm) ≥ 16 can predict moderate and sever OHSS with sensitivity 88.9% specificity 82%, PPV 53.8%, NPV 89.2%, and accuracy 82.5%.
In comparison between accuracy of AMH and AFC for prediction of OHSS ,AMH was more accurate as apredictive marker of OHSS.
Finally, there is not significant relationship between high basal AMH levels in OHSS group and pregnancy rate demonstrated in our study raises the hypothesis of a negative link between AMH and final oocyte maturation.
AMH measurement and AFC prior to COH can provide useful information to direct the application of mild friendly stimulation protocols in order to avoid OHSS and to tailor the ideal protocol.
Both AFC and AMH have some disadvantages. The AFC necessitates skilled ultrasound operators who carefully identify, measure, and count ovarian follicles. There is a moderate intercycle and interobsrever variability in AFC. On the other hand, in some country AMH assay is not routinely available. The availability of the AMH assay may present some problems but surely this test system will soon become part of one of the large automated platform. |
