Research Review: How to Reduce Premature Luteinization (PL) in Women 43 and Older Undergoing IVF

You might notice this post is a bit shorter than my others, you are correct! I am streamlining my look 😉 In all seriousness, I am super excited to be making this change. Once a week, I will be posting a review on an article specifically related to women trying to conceive with advanced maternal age (AMA). It’s thorough, it’s important, it’s quick and I can cover a lot more information.

Also, I have a secret… a new project. I am so excited I could burst! More details coming soon… Now let’s get into this!

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Women ages 43 and above have a much greater rate of premature luteinization (PL). The Center for Fertility and Health (CFH) in Oslo Norway confirmed that performing oocyte retrievals at an earlier than standard time significantly improves the negative impacts of PL in women 43 and older.

Premature Luteinization is AKA Premature Follicular Phase Progesterone Rise (pFPPR)

Premature Luteinization is a term that refers to a premature surge in luteinizing hormone (LH). Kaponis describes the need to replace the term with one that more accurately describes the process. Today, a premature rise in progesterone should be eliminated when protocols use gonadotrophin releasing hormone (GnRH) due to its ability to suppress gonadotrophin production, but the rise still happens. Kaponis argues that this phenomenon renders the term premature luteinization inadequate. When you read about PL, keep in mind that a premature LH surge is being discounted as the primary cause for premature progesterone rise.

In my experience, this adequately describes my IVF retrieval cycle. I was unable to do a fresh transfer because my progesterone was already 2.0 on the day of HCG adminstration (trigger day) despite the fact that my LH was very low due to daily injections of Cetrotide to prevent LH production. In my case, LH did not cause PL.

Background:

Granulosa cells (GC) are a type of cell in your ovaries that produce hormones including estrogen and progesterone. As women age, GC function decreases which may cause an elevated P4/E2 ratio, this is the ratios of progesterone to estrogen. An elevated P4/E2 ratio is a well-known marker of pFPPR and causes LH to surge before your oocytes are ready for the final step in maturation.

Study Details:

Wu and colleagues conducted studies to evaluate the cause of pFPPR. In the first study, they compared expressions of molecular markers, enzymes and genes from cycling women in their 20s, 30s and 40s. Results showed the P4/E2 ratio to be significantly higher in women 43 yo and above.

In the second study, oocyte and hormonal parameters were compared in two groups of women 43 yo and older. Both groups underwent IVF:

Group 1: oocytes were retrieved at the standard time, i.e. when the leading follicle size was 19-21mm

Group 2: oocytes were retrieved at an earlier than standard time, i.e. when the leading follicle was 16mm

Results

Results showed significantly less oocyte degeneration in Group 2, the earlier retrieved group. Interestingly, Group 2 had more immature oocytes, but a higher number of good quality embryos. Further studies revealed early retrievals significantly decreased P4/E2 ratios compared to retrievals done at the standard time.

Wrap Up:

Premature FPPR in women of advanced age was associated with rapidly declining IVF pregnancy rates. Compared to standard timed retrievals in women of similar age, earlier retrieved patients exhibited improved embryo numbers, quality and clinical pregnancy rates. If pFPPR can be avoided by earlier oocyte retrieval, IVF outcomes will be improved.

Thank you so much for being here,
<3 BK

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Kaponis, Apostolos et al. “The curious case of premature luteinization.” Journal of assisted reproduction and genetics vol. 35,10 (2018): 1723-1740.

Wu, Yan-Guang, et al. “Aging-Related Premature Luteinization of Granulosa Cells Is Avoided by Early Oocyte Retrieval.” Bio Scientifica, Bioscientifica Ltd, 1 Sept. 2015.