Why is progesterone so important?

Progesterone is the hormone responsible for the development of structural and biochemical changes at the endometrial level that allow the endometrium to be receptive, known as the window of implantation. But it also has other functions: it has a modulating effect on immunity at both the uterine and uterine level.

It also has a uterine relaxant effect, reduces contractility and promotes utero-placental circulation. An adequate level of progesterone contributes to the success of the treatment by 10-15% per cycle. All this has led to a growing interest in this hormone in recent years, and progesterone has become the star hormone in human reproduction.

Increase in the number of cryotransfers.

Over the last decade, improvements in vitrification techniques have made it possible to carry out an increasing number of cryotransfers for various reasons:

1. To avoid the development of ovarian hyperstimulation syndrome.
2. The age of the patients makes it advisable to carry out genetic studies on the embryos before transfer, or certain pathologies such as endometriosis, adenomyosis, polycystic ovary that benefit from a delayed transfer.

This cryotransfer can be carried out in a natural cycle or by means of medication, known as a substituted cycle. In recent years

several authors point out the importance of measuring the progesterone level both before the transfer and on the day of the pregnancy test to improve the reproductive results.

Monitoring of progesterone levels in the natural cycle

Dr Gaggiotti’s group (1) observed that women with regular cycles who transfer in a natural cycle have in 37% of cases a low progesterone level on the day of transfer of less than 10ng/ml, which is associated with a worse gestation rate and a higher incidence of miscarriage. Therefore in our centre we decided to supplement with progesterone 200mg every 12 hours to all these patients in order to maintain an adequate level and improve the results.

Monitoring of progesterone levels in a medicated cycle

Something similar occurs in substituted cycles, despite supplementing with progesterone, one third of patients have a low progesterone level on the day of transfer below 10ng/ml, which is again associated with worse gestation rate, lower live birth rate and higher incidence of miscarriage, even when genetically normal embryos are transferred (2,3). Since 2020 in our centre we measure progesterone the day before transfer and if it is less than 10ng/ml, we supplement with subcutaneous progesterone, one injection per day.

Should we monitor beyond the moment of transfer?

It should also be noted that, after implantation, i.e. after having obtained a positive pregnancy test, we should also monitor the progesterone level, as again 30% of patients who had an adequate level of progesterone prior to transfer and have a positive test have a level below 10ng/ml, and this is associated with a greater probability of miscarriage, as Dr Alsberg points out (4). Again in these cases subcutaneous progesterone supplementation is performed.

Progesterone level monitoring in patients with endometriosis/adenomyosis

There is a group of patients who also have resistance to progesterone at the receptor level: patients with endometriosis and adenomyosis, who even with progesterone levels in the normal range benefit from greater supplementation, as it has been shown that if on the day of the pregnancy test their progesterone level is higher than 37ng/ml (5), they will have a better rate of live newborns. Therefore, it is essential to personalise each case and adjust the most appropriate therapy to obtain the best results.

Bibliography

1. Marré SG, Alvarez M, Gonzalez Foruria I, Parriego M, Garcia S, Martinez F, PN Barri, Polyzos N, Coroleu B. Low progesterone levels on the day before natural cycle frozen embryo transfer are negatively associated with live birth rates. Hum Reprod.2020;7:1623-1629. doi:10.1093/humrep/deaa092
2. Labarta, E., Mariani, G., Holtmann, N., Celada, P., Remohi, J., Bosch, E. Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Human reproduction (Oxford, England) 2017; 32: 2437–2442.doi:10.1093/humrep/dex316
3. Gaggiotti-Marre, S., Martinez, F., Coll, L., Garcia, S., Álvarez, M., Parriego, M., Barri, P.N., Polyzos, N., Coroleu, B. Low serum progesterone the day prior to frozen embryo transfer of euploid embryos is associated with significant reduction in live birth rates. Gynecol. Endocrinol. 2018: 1–4. doi:10.1080/09513590.2 018.1534952
4. Alsbjerg, B., Thomsen, L., Elbaek, H.O., Laursen, R., Povlsen, B.B., Haahr, T., Humaidan, P. Progesterone levels on pregnancy test day after hormone replacement therapy cryopreserved embryo transfer cycles and related reproductive outcomes. Reprod. Biomed. Online 2018; 37: 641–647. doi:10.1016/j. rbmo.2018.08.022
5. Alsberg B, Kesmodel VS, Humaidan P. Endometriosis patients benefit from high serum progesterone in hormone replacement therapy frozen embryo transfer cycles: cohort study. Reprod Biomed Online.2023;46:92-98.