Anti-Müllerian Hormone (AMH) is A Good Predictor for Ongoing Pregnancy in Women Undergoing IVF/ICSI in Antagonist Cycles

Anti-Mullerian hormone (AMH) is a member of the TGF-beta family and is expressed by the small preantral and early antral follicles. The AMH level reflects the size of the primordial follicle pool and the best biochemical marker of ovarian function across an array of clinical situations [1]. In adult women, AMH levels gradually decline as the primordial follicle pool declines with age [2]. The AMH level appears to be an early, reliable, direct indicator of declining ovarian function. In patients planning IVF, an AMH level correlate with the number of oocytes retrieved after stimulation, and is the best biomarker for predicting poor and excessive ovarian response [3,4].

Oocyte retrieval was done 36 hours after Ovitrelle (hCG)/ Suprefact®GnRH triggering, and a transfer was done at day 2 or day 5. Luteal support was given using vaginal progesterone Lutinus® 100mg 3 times daily for 2 weeks. Lutinus® All data were prospectively collected and recorded in an SSPS version 22 and STATA 13.1. database. The study was approved by the Danish Patient Safety Authority (Number 3-3013-2242/1).
2. Statistics, comment in text. Table 2 shows first cycle response parameters and clinical outcome in the three AMH groups. The ongoing pregnancy rates per started cycle in the three AMH groups were 15%, 25% and 38%, respectively (p<0.001) and per transfer 21%, 30% and 48% respectively (p<0.001). The chance of achieving an ongoing pregnancy was reduced in women with low AMH, whereas high AMH was associated with an increased chance of achieving an ongoing pregnancy.  Table 3 shows response parameters and clinical outcome for all cycles 2148. The ongoing pregnancy per started cycle in the AMH groups were 14%, 22% and 32% respectively (p<0.001) and per transfer 20%, 26% and 38 respectively (<0.001). In the first cycle, the pregnancy rate is high compared to all cycles. The pregnancy rate is low after the first cycle, but if we are based on the AMH group, there is still significant pregnancy rate between AMH groups. The pregnancy rate is high in the group with high AMH and low in the group with low AMH.  Table 4 shows the pregnancy rate the relationship to the first cycle and the second or more cycle based on AMH and age. In the first cycle, age did not affect pregnancy relative to AMH groups. The pregnancy rate was significantly high in groups with high AMH, while in patients>35-years-old pregnancy rate was generally low, but still significantly high in groups with high AMH. In the second or more cycle of patients ≤35-yearsold, age had no influence, and patients with high AMH had a high pregnancy rate. Patients >35-years-old in second or more cycle had no significant difference in pregnancy rate between AMH groups.

Discussion
The present study provides results from 2148 ART cycles where a stimulation based on the AMH level FSH dosing algorithm. The main findings of the present study were patients with AMH levels above 32pmol/L and thus a predicted high rate of pregnancy. Several studies based on the number of oocytes that predict high pregnancy rates [16][17][18][19]. We know that patients with high AMH can develop more follicles, and as a result, many oocytes come with aspiration. It has always been difficult to keep the balance between having a high pregnancy and minimizing OHSS. Patients with anovulation have high AMH and tend to have many follicles on stimulation, but they may also have a low response if stimulated with an inadequate dose of FSH [20][21][22]. In our study we could show that patients with high AMH, even some of them, do not have many oocytes nevertheless, had better pregnancy rate in the first cycle regardless of age. In patients >35-year-old, the rate of pregnancy decreases but is still present, for patients with high AMH has a high pregnancy rate compared to patients with low AMH.
Patients who had completed number two or more cycles pregnancy is still high in the group of patients with high AMH aged <35 years. In patients aged>35 years, with two or more cycles we could not find different inter-group pregnancy rates, regardless of AMH level. AMH is a very good predictor of pregnancy prognosis. Patients with high AMH are at risk group for OHSS therefore we choose AMH algorithm to minimize OHSS and maintain good pregnancy rate. We have mildly stimulated patients with AMH> 32 where some of the patients have responded with very few follicles but the pregnancy rate was satisfactory and none of them had OHSS [23][24][25]. Several studies show that a number of oocytes 8-14 will provide better pregnancy rate [16][17][18]. We agree that patients with high AMH and young age can reach in most cases the number of oocytes we want. Our study confirms that AMH is a really good prediction for oocytes retrieval and pregnancy rate, especially in patients <35 years-old , whatever there is a first, second or more cycle.
Low AMH patients do not have a good pregnancy prognosis, the number of oocytes retrieval is not high and the pregnancy rate is low [26][27][28][29][30]. Our study shows that even though age was <35 years, the patients with low AMH had significant low pregnancy compared to patients with high AMH. AMH level reflects pregnancy chances in all groups, we can see differences in pregnancy rate in all AMH groups. Group of patients with AMH <12pmol/L had poor pregnancy and group of patients with AMH> 32pmol/L had the best pregnancy rate. Patients with AMH 12-32pmol/L normal responder stimulated with standard dose FSH, the pregnancy rate was better than the group of patients with low AMH, but low compared to the group of patients with high AMH> 32pmol/L.

Conclusion
The main finding suggest that an AMH is a good predictor for pregnancy prognosis in patients at the least <35 years old. Patients with high AMH have a significantly better pregnancy rate compared to patients with low AMH. The AMH algorithm can be used to select the starting dose of FSH to minimize OHSS and retains good pregnancy rate. However, a randomised study with enough power with our protocol should be performed