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High Live Birth Rates in IVF High Responders Using Either a Lupron Trigger Alone (agonist trigger) or Using a Dual Trigger if Intensive Luteal Support is Given


Research study presented by Richard Sherbahn, MD at the 70th Annual Meeting of the American Society for Reproductive Medicine, Honolulu, HI, October, 2014.


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What is ovarian hyperstimulation syndrome - OHSS?

  • A condition with enlarged ovaries, lower abdominal bloating and discomfort and fluid accumulation in the abdominal cavity
  • It can occur after ovarian stimulation for in vitro fertilization when there is a high response to medications with many growing follicles
  • Women with polycystic ovaries are at higher risk for developing ovarian hyperstimulation syndrome after IVF

What is a Lupron (or agonist) trigger?

  • Use of Lupron (a GnRH agonist medication) instead of HCG (traditional method) to trigger final maturation of the follicles and eggs for IVF
  • A Lupron trigger (also called an "agonist" trigger) can eliminate or dramatically reduce the risk of ovarian hyperstimulation syndrome

What have other studies shown regarding using Lupron triggers to prevent hyperstimulation?

Results from other studies have been mixed. They consistently show a large reduction (or elimination) of ovarian hyperstimulation risks, but the IVF success rates have been variable. Some studies report good success rates with an agonist trigger and other studies show much lower success rates.


Our study on Lupron triggers with and without supplemental HCG
Study authors: Richard Sherbahn, MD and Michelle Catenacci, MD


Objective:

To investigate IVF live birth rates, pregnancy loss rates and ovarian hyperstimulation occurrence rates in high responders that had a pure Lupron trigger vs. a dual trigger with Lupron and a small dose of HCG.

Study Design and Methods

  • Retrospective chart review
  • All 135 women under age 38 using their own eggs for IVF and who received either a pure Lupron trigger or a Lupron trigger plus 1500-2000 units of HCG between November 2011 and July 2013 were included
  • Patients were put in 2 groups based on their trigger injections (pure agonist trigger or dual trigger)
  • Intensive luteal support was given using intramuscular progesterone and oral or transdermal estradiol
  • Serum levels of estradiol and progesterone were monitored in the luteal phase and into early pregnancy
  • Cycle outcomes were compared and Chi-square, Fisher's exact test and T-tests were used for statistical analysis

Results

Lupron trigger table of data for 2 groups in study

Values expressed as either percentage or mean ± SD

  • The 2 groups had similar characteristics other than significantly higher AMH levels and resting antral follicle counts in the pure agonist trigger group
  • The mean number of eggs retrieved, pregnancy loss rates, live birth rates and rate of OHSS development were not significantly different between the pure agonist trigger group and the dual trigger group
  • The live birth rate per egg retrieval was 52.6% in the pure agonist trigger group and 64.4% in the dual trigger group
  • The difference was not statistically significant. There was a trend for higher pregnancy loss rates in the pure agonist group (not significant)

When the pure agonist trigger group was split into 2 groups with peak estradiol < 4000 pg/ml vs. > 4000 pg/ml the live birth rate was significantly higher (p < 0.05) in the group with estradiol > 4000 pg/ml (19/45, 42.2% vs. 21/31, 67.7%).

Lupron trigger study data for patients with E2 <4000 vs. >4000

Values expressed as either percentage or mean ± SD


Discussion

  • Previous studies of agonist triggers have shown inconsistent results
  • In 2005, Humaidan et al.(1, reference below) showed a very low clinical pregnancy rate of 6% with agonist trigger versus 36% with HCG. They showed an early pregnancy loss rate of 79% with agonist trigger versus 4% with HCG trigger. Vaginal Crinone (90 mg per day) and 4 mg per day of oral estradiol were given until only day 12 after embryo transfer.
  • In 2008, Engmann et al. (2, reference below) published a prospective randomized trial of agonist triggers vs. HCG triggers in patients at risk for OHSS. Using intensive luteal support in the agonist trigger group they had equivalent ongoing pregnancy rates in the 2 trigger groups.
  • In 2011, a Cochran review by Youssef et al. (3, reference below) concluded that an agonist trigger should not be routinely used due to the significantly lower live birth rate.
  • We obtained excellent live birth rates after using a Lupron trigger with intensive luteal support. Our results are similar to those of Engmann et al. (2, reference below)

Why do our results differ from other studies?

  • Other studies on Lupron triggers (and other agonist drug triggers) have shown inconsistent results
  • Some have shown high success rates while others have shown low success rates
  • In the studies that showed low success rates the agonist triggers were not followed up with sufficient estrogen and progesterone support after the trigger was given
  • We believe that this support needs to be aggressive and should be continued through the first trimester of pregnancy to increase pregnancy rates and reduce miscarriage rates

Conclusions

  • Live birth rates with IVF using a pure agonist trigger can be high when intensive luteal support is given.
  • Live birth rates using a pure agonist trigger are higher when the peak estradiol is > 4000 pg/ml.
  • If the peak estradiol is under 4000 pg/ml consideration should be given to using a dual trigger with 1500 IU of HCG.
  • We believe that the reduced success rates with pure agonist triggers and lower peak estradiol levels are mainly due to inadequate progesterone and estradiol support in the luteal phase and in early pregnancy.
  • Proper use of Lupron (or other agonist) triggers can result in excellent IVF success rates and no ovarian hyperstimulation (with pure Lupron trigger), or rare hyperstimulation cases when a dual trigger with a low dose of HCG is given.

References:

1. Humaidan, P., Bredkjaer, H.E., Bungum, L., Bungum, M., Grøndahl,M.L., Westergaard, L., Andersen, C.Y., 2005. GnRH agonist (buserelin) or HCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum. Reprod.20, 1213–1220.

2. Engmann, L., DiLuigi, A., Schmidt, D., Nulsen, J., Maier, D., Benadiva, C., 2008. The use of gonadotropin-releasing hormone(GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study. Fertil.Steril. 89, 84–91.

3. Youssef, M.A., Van der Veen, F., Al-Inany, H.G., et al.2011. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles. Cochrane Database Syst. Rev., 2011; Jan 19;(1):CD008046.


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