Large trial examines impact of growth hormone on IVF success

A new randomized controlled trial investigated the use of growth hormone (GH) in normal responders, finding no differences in IVF and pregnancy outcomes.

Women with a poor ovarian response to ovarian stimulation have few eggs retrieved, which is often related to low ovarian reserve (low AMH).

Growth hormone (GH) is secreted by the pituitary gland and leads to synthesis of insulin-like growth factor 1 (IGF-1) in the liver. IGF-1 receptors are present on egg cells and the surrounding granulosa and theca cells in the follicle, and can assist in the process of egg maturation. For this reason, GH is often used during ovarian stimulation for poor responders and may improve the quantity and quality of eggs retrieved (Hart 2019).

Much of the existing research for GH is based on poor responders, and there isn’t much data for normal responders. Some have suggested that GH be used universally in all IVF patients. This post is a summary of a study by Mourad et al. (2024), who conducted a randomized controlled trial (RCT) investigating the use of GH in normal responders (average AMH 2.51 ng/ml).

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Study details

This section covers key details of how the study was performed, including patient characteristics, how they were treated, and other methods used. For those who aren’t interested in these details, and just want to see the results, you can go ahead and skip this part.

• This was a randomized controlled trial that took place at a single IVF center in Canada between 2014 and 2020.
• Participants received 2.5 mg daily of GH (Saizen) subcutaneously, starting on the first day of ovarian stimulation to trigger day (ie. for about 11-12 days before trigger). This equates to about 7.5 IU of GH (based on info from this pdf).
• This study was funded mostly by EMD Serono, the manufacturer of Saizen. Typically, when a company funds a study, there’s a concern they might influence the results to benefit sales of their product, but we probably don’t have to worry about that here. We’ll talk about this more at the end.
• Inclusions: women aged 30-42 with primary or secondary infertility, GNRH antagonist protocol.
• Exclusions: BMI 35 or above, AMH <0.5 ng/ml, recurrent implantation failure, no PGT-A.
• Day 3 or day 5/6 embryos were transferred. Only good quality embryos were transferred. It was not specifically stated how many embryos were transferred, and I suspect this is because it was individualized to each patient based on their age.
• The primary outcome was the clinical pregnancy rate.

In terms of sample size, there were 288 patients that were randomized to the GH and no GH groups. Each group had 39 drop outs (27% dropout rate). In the end, there were 105 participants in both the GH and no GH groups (210 in total). They assumed a 50% increase in pregnancy rate (ie. 30% to 45%), requiring 288 patients for 80% statistical power. The authors described this study as the largest performed to date in normal responders.

In terms of baseline characteristics, the average age of the participants was 38, they were normal responders (AMH 2.51 ng/ml), about half had primary or secondary infertility, and about half were doing their first IVF cycle or had done IVF before. They had similar doses of gonadotropins, stimulation days, endometrial thickness on trigger day, frozen/frozen transfers, IVF/ICSI, etc.

Growth hormone treatment had no effect on IVF, pregnancy outcomes in normal responders

In this study, participants were either administered growth hormone (GH) prior to their trigger day or they received no GH treatment. In terms of IVF outcomes:

• No differences in the number of follicles (<15 mm and 15 mm or larger).
• No difference in the cycle cancellation rate.
• No difference in the number of eggs retrieved.
• No difference in the number of mature eggs, or the egg maturation rate.
• No difference in the fertilization rate, or the number of cycles with failed fertilization.
• No difference in the number of embryos available for transfer. There was also no difference in the % of cycles that had all embryos discarded due to poor quality.

Either a fresh embryo transfer or a frozen embryo transfer was done. The primary outcome of this study was the clinical pregnancy rate. There was no difference for GH vs no GH for both the fresh transfer or the first frozen transfer (44% vs 50%, p= 0.406, rate difference [95% CI]: -0.06 [-0.22, 0.09]; 35% vs 44%, p= 0.356, -0.09 [-0.28, 0.10]).

For the other fresh/frozen transfer outcomes, there were:

• No differences in the implantation rate.
• No differences in the miscarriage rate.
• No differences in the live birth rate.
• For the fresh transfer group, on average the GH group transferred 3.0 embryos and the no GH group transferred 2.5 embryos*. There were no differences in the % of day 3 or day 5/6 embryos transferred.
• For the fresh transfer group, on average the GH group transferred 3.1 embryos and the no GH group transferred 2.4 embryos*. There were no differences in the % of day 3 or day 5/6 embryos transferred.

*This is an unusual way to report the number of embryos transferred, but it helps to focus on the number of embryos that led to a clinical pregnancy. They didn’t report whether these were statistically different or not, so they might have been. If there were differences, the GH group had more embryos transferred but still experienced a lower clinical pregnancy rate. This suggests that despite transferring additional embryos in the GH group—which theoretically could increase the likelihood of pregnancy—the use of GH did not improve the chances of achieving a clinical pregnancy.

Since this was an RCT, they reported both the intention-to-treat and per-protocol results. There were no differences.

Conclusions

Overall, there were no differences for GH in normal responders.

For IVF outcomes, there were no differences in the number of follicles, number of eggs retrieved, fertilization rate or the number of embryos available for transfer.

For embryo transfer outcomes, there were no differences in the clinical pregnancy or live birth rates, or miscarriage rates.

I would have liked to see some subgroup analyses in this study — they included a broad age range (30-42) and there may have been differences in outcomes for younger or older patients.

Growth hormone is also primarily used in poor responders, and this study only included patients with a normal ovarian response (average AMH was 2.51 ng/ml). One meta-analysis combined the results of multiple studies involving GH and poor responders, finding that it can increase the number of eggs retrieved. Another meta-analysis found improved pregnancy outcomes and number of eggs retrieved with GH in poor responders, but no difference in normal responders.

This study wasn’t designed to look at poor responders though, and was primarily meant to look at patients with a normal response. GH can sometimes be used in patients with a normal response, and has been suggested to be used universally for all patients undergoing IVF. This study (and others) show that there’s no benefit for these patients.

The study was designed to detect larger differences in clinical pregnancy rates (ie. from 30% to 45%), which means smaller effects of GH in normal responders may not have been identified with the number of patients they had.

This study was funded by EMD Serono, who manufactures GH and provided the GH for the study and paid for data analysis. While company funding usually raises concerns about potential bias to promote their product, the fact that the study’s results showed no benefit from using GH suggests that the findings were reported honestly.

Related studies

To learn more about this topic, you can check out a number of studies referenced in this study below (4 links):

Reference

Ali Mourad, Wael Jamal, Robert Hemmings, Artak Tadevosyan, Simon Phillips, Isaac-Jacques Kadoch, Empirical use of growth hormone in IVF is useless: the largest randomized controlled trial, Human Reproduction, 2024;, deae251, https://doi.org/10.1093/humrep/deae251

 

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.

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