Meta-Analysis looks at hormone pre-treatment (Lupron Depot) for IVF with endometriosis

A meta-analysis combined the results of 9 studies that looked at hormone pre-treatment (like Lupron Depot) in patients with endometriosis and found no clear benefit. Most of the patients were diagnosed and surgically treated by laparoscopy before hormone pre-treatment.

For patients with endometriosis, getting pregnant can be more challenging. Hormone pre-treatment (ie. Lupron Depot) is sometimes used before IVF to suppress estrogen that fuels the growth of endometriosis. This may help reduce inflammation to improve the uterine environment and egg quality before starting IVF.

These medications can be taken as a short course (about 1 month before starting IVF, known as a “long” protocol) or as a longer course (3 months before IVF, known as an “ultralong” protocol). Some clinics also use progestins, such as dienogest or medroxyprogesterone acetate (MPA), which are synthetic forms of progesterone that are often better tolerated and help counteract estrogen to suppress endometriosis.

While these approaches are commonly used, it’s not clear if they actually improve IVF success rates. This post is a summary of a network meta-analysis by Riemma et al. (2025), who combined the results of 9 randomized controlled trials (RCTs) that investigated hormone pre-treatments on women with endometriosis having IVF:

• No hormone pre-treatment (control)
• Long GnRH agonist pre-treatment (typically ~1 month), involving daily buserelin nasal spray or a single depot triptorelin injection for 1 cycle before ovarian stimulation.
• Ultralong GnRH agonist pre-treatment (3 months), typically involving monthly doses of 3.75 mg depot injections of leuprorelin (Lupron Depot), triptorelin, or goserelin.
• Progestins (like dienogest or MPA)

All the studies in this meta-analysis used laparoscopy to diagnose endometriosis, and most included surgical treatment during the procedure, reflecting standard practice. Two studies didn’t specify if surgery was done, but it was likely performed in some patients. As a result, these findings primarily apply to patients diagnosed by laparoscopy who underwent surgical treatment for endometriosis. For those who have not received surgical treatment, the relevance of these results are unclear.

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Study details

• Nine RCTs were included, published between 2002 and 2022, with 2087 women overall.
• Studies were conducted in Europe, Asia, North America, and Egypt.
• Common themes in the inclusion criteria were age <40, regular menstrual cycles, and no diminished ovarian reserve or other major reproductive issues like PCOS or adenomyosis.
• Endometriosis was defined according to the rASRM staging system, ranging from stage I (mild) to stage IV (severe).
• A “network” meta-analysis was used, which lets you combine studies that have different treatment protocols that aren’t directly compared. Check the glossary for “meta-analysis” for more info.

The studies and treatment types included were:

• Guo et al. (2022) — Note that this study was recently retracted due to its similarity to another submission by the same research group. However, this is unlikely to affect the overall results of the meta-analysis.
• Tomassetti et al. (2021)
• Khalifa et al. (2021)
• Rodriguez-Tarrega et al. (2020)
• Kaponis et al. (2019)
• Tamura et al. (2019)
• Decleer et al. (2016)
• Rickes et al. (2002)
• Surrey et al. (2002)

No difference in pregnancy outcomes with hormone pre-treatments

Now let’s check out the results! Here, I’ll explain the overall results from the network meta-analysis and also report the SUCRA scores (a higher SUCRA % indicates that the treatment is better, see the glossary for more info).

Clinical pregnancy rate. Based on the 9 studies that reported clinical pregnancy rate in the meta-analysis, there were no statistically significant differences between any of the treatments vs no treatment. The SUCRA scores were all similar to no treatment.

Live birth rate. Based on the 4 studies that reported live birth rate in the meta-analysis, there were no statistically significant differences between any of the treatments vs no treatment. SUCRA ranked no treatment as the best option (50%), followed by long GnRH agonist, progestins and ultralong GnRH agonist (36.6%, 7.0%, 6.4%).

Pregnancy loss rate. Based on the 5 studies that reported pregnancy loss rate in the meta-analysis, there were no statistically significant differences between any of the treatments vs no treatment. SUCRA ranked no treatment as the best option (57.9%), followed by long GnRH agonist, ultralong GnRH agonist and progestins (18.4%, 12.3%, 11.4%).

Implantation rate. Based on the 3 studies that reported implantation rate in the meta-analysis, there were no statistically significant differences between any of the treatments. SUCRA ranked long GnRH agonist as the best option (45.0%), followed by ultralong GnRH agonist and progestins (39.5%, 15.5%). The no treatment group wasn’t included in these studies and therefore could not be ranked.

The researchers also performed subgroup analyses to examine outcomes in different patient groups. I won’t report all the data here, but based on endometriosis stage:

• For both mild (I–II, 2 studies) and severe (III–IV, 2 studies) endometriosis, no clear benefit of any treatment was found
• In mild cases, no treatment ranked highest (SUCRA 60.4%)

Conclusions

This meta-analysis found that long or ultralong GnRH agonist treatments and progestins did not lead to improved outcomes for patients with endometriosis.

It’s important to note that most patients had already had surgery in this meta-analysis, which may have improved outcomes on its own, making it harder to see any added benefit from medication. Some control groups included patients who didn’t receive the medications, but they had still undergone surgery. Studying patients who receive no treatment at all is difficult for ethical reasons. This is a common challenge in research — without a fully untreated group, it’s difficult to know whether a treatment really helps.

While there doesn’t appear to be a benefit from hormone pre-treatment in endometriosis patients who have been diagnosed and surgically treated with laparoscopy, it’s unclear whether these results apply to patients who haven’t received laparoscopy. Endometriosis can also be diagnosed without surgery using methods like ultrasound or ReceptivaDx, though these are generally seen as less reliable than laparoscopy (read more about non-surgical methods of diagnosing endometriosis here).

Some limitations of this research include:

• Small number of studies and modest sample sizes.
• Wide variation in endometriosis severity (I–IV), and treatment protocols.
• Potential role of adenomyosis wasn’t explored, despite being common in endometriosis patients and potentially responsive to GnRH agonists.
• They also didn’t look at different outcomes that reflect egg quality.
• It’s unclear how much time had passed between patients’ surgeries and their enrollment in the study.

While this study didn’t find clear benefits from hormone pre-treatment overall, it’s possible that certain groups of patients, such as those with more severe endometriosis or adenomyosis, may still benefit in ways that weren’t captured here. Treatment should always be tailored to the individual, and it’s important to speak with your doctor to decide what’s best for your specific situation.

Reference

Riemma G, Cobellis L, Laganà AS, Etrusco A, Della Corte L, Torella M, Vastarella MG, Carotenuto RM, De Franciscis P. Efficacy of hormone pre-treatment before ART to improve reproductive outcomes in infertile women with endometriosis: Network meta-analysis of randomized controlled trials. Int J Gynaecol Obstet. 2025 Apr 12. doi: 10.1002/ijgo.70134. Epub ahead of print. PMID: 40221832.

 

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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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