**9. Timing of starting luteal support**

164 Enhancing Success of Assisted Reproduction

to 1.67). The results for miscarriage and multiple pregnancy did not indicate a difference of effect. The authors concluded that there were significant results showing a benefit from addition of GnRH- a to progesterone for the outcomes of live birth, clinical pregnancy and ongoing pregnancy. In another recent systematic review and meta-analysis [57] six relevant RCTs were identified including a total of 2012 patients. The probability of live birth rate (risk difference : +16%, 95% CI: +10 to +22%) was significantly higher in patients who received GnRH agonist support compared with those who did not. The subgroup analysis according to the type of GnRH analogue used for LH suppression did not change the effect observed (studies in which GnRH agonist was used during ovarian stimulation, risk difference : +15%, 95% CI: +5 to +23%); (studies in which GnRH antagonist was used during ovarian stimulation, risk difference : +19%, 95% CI: +11 to +27%). The conclusion of the study was that the best available evidence suggests that GnRH agonist addition during the

The use of hCG is driven by the hypothesis that, in addition to progesterone and estrogen, the corpus luteum produces other hormones which are required for endometrial transformation and optimization of the conditions for embryo implantation and development. Some randomized trials supported the use of hCG for luteal support [58 ,59].However one randomized controlled trial [60] where patients at ovum pick –up were randomized to receive luteal support as either progesterone only or hCG only or combination of progesterone and hCG showed that there were no statistically significant differences with regard to the main outcome parameter, the clinical ongoing pregnancy rate .However using a standardized discomfort scale, there were more complaints towards the end of the luteal phase in the groups receiving hCG only or an additional injection of hCG, when compared to the progesterone only groups .The conclusion of the study was that progesterone only for luteal phase support leads to the same clinical ongoing pregnancy rate as hCG, but has no impact on the comfort of the patient. Furthermore two meta-analyses [18 ,19] found no statistically signicant differences in clinical pregnancy, ongoing pregnancy, and miscarriage rates between progesterone and hCG. The odds ratio of OHSS was more than threefold higher when hCG was added to the luteal phase support regimen, conrming that progesterone alone is a better strategy. In the most recent Cochrane review and meta-analysis [21], 15 studies, including 2117 women investigated progesterone versus hCG regimens. The hCG regimens were sub grouped into comparisons of progesterone versus hCG and progesterone versus progesterone + hCG. The results did not indicate a difference of effect between the interventions, except for OHSS. Furthermore subgroup analysis of progesterone versus progesterone + hCG showed a significant benefit

The use of a GnRH agonist is an integral part of long protocols used in IVF/ICSI cycles and it results in pituitary suppression and luteal phase deficiency with decline in serum

luteal phase significantly increases the probability of live birth rates.

**7. Human chorionic gonadotropins (hCG)** 

from progesterone (Peto OR 0.45, 95% CI 0.26 to 0.79).

**8. Estrogen** 

In stimulated IVF/ICSI cycles, the steroid production in the first week after oocyte retrieval is likely to be well timed and more than sufficient, so the start of exogenous support is not apt to be critical within this window. It was reported that pregnancy rates were higher in IVF when progesterone was started three rather than six days after oocyte collection [67] .A randomized controlled trial [68] allocated 130 patients to start luteal support at hCG day and , 128 at egg retrieval day and 127 at day of embryo transfer. Ongoing pregnancy rate of 20.8% was found in the hCG-day group versus 22.7 and 23.6% in the other two groups, respectively. This study showed that , there is no difference between the three different times of start of luteal support.
