Testosterone Levels Linked to Fertility in Severe Endometriosis

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Testosterone levels linked to fertility in severe endometriosis

Low basal serum testosterone level is detrimental to the embryo implantation in the patients with severe endometriosis

A retrospective cohort study was carried out to investigate the potential effects of (basal) serum testosterone levels, on ovarian response and IVF outcomes, in women with stage III-IV endometriosis according to the revised American Society for Reproductive Medicine classification system.

One thousand and sixty eight women diagnosed with endometriosis via laparoscopic surgery were reviewed for eligibility. Women undergoing their first IVF/ ICSI cycle where oocyte pick up could be performed were included while women also diagnosed with adenomyosis, polycystic ovarian syndrome, hyperprolactinemia, adrenal disease, irregular menstrual cycles, aged > 39 or undertook preimplantation genetic testing were excluded.

Ovarian stimulation was carried out using the long GnRH‐agonist protocol or GNRH-antagonist protocol. FSH dosage was based on age, weight and ovarian reserve. Monitoring was carried out via transvaginal ultrasound and blood hormone levels. When at least 2 follicles reached a diameter > 18µm (or more than 2 follicles diameter > 17µm) a trigger shot of human chorionic gonadotropin was administered and oocyte retrieval carried out 34-36 hours later.

Standard IVF or ICSI was performed with embryos cultured for 3 or 5 days before being transferred. Up to 3 embryos were transferred at a time depending on embryo quality, development stage and history of uterine surgery. Luteal support (progesterone) was given to women undergoing a fresh embryo transfer. Urine and serum HCG levels were then checked 2 weeks following transfer, with positive results confirmed by ultrasound 2 to 3 weeks later for clinical pregnancy.

For comparison number of retrieved oocytes, two pronuclei (2PN) embryos, available embryos and high quality embryos per patient was recorded. Number of gestational sacs divided by number of embryos transferred defined the implantation rate. Multiple pregnancy was noted if more than one fetus was present during the 6th week ultrasound. Loss of a clinical pregnancy before 28 weeks was recorded as miscarriage, while the birth of a viable infant after 28 weeks gestation was defined as a live birth.

Of the 1068 initial women, 407 with stage III-IV endometriosis met the inclusion / exclusion criteria. Baseline characteristics showed that serum basal testosterone levels was significantly higher among the pregnant group compared to the non-pregnant group (0.37 ±0.34 vs 0.33 ±0.18 ng/mL).

Similarly, number of oocytes retrieved (10.76 vs 9.23), 2PN embryos (7.30 vs 6.23) and high quality embryos (3.30 vs 2.62) was also statistically higher among the pregnant group.

Interestingly detailed correlation analysis found that basal serum testosterone was not linked to basal LH levels, number of oocytes retrieved, 2PN embryos or the number of high quality embryos after adjusting for age.

An optimal cut-off value, for basal serum testosterone, of 0.305 ng/mL was identified. Using this cut-off value, logistical regression analyses showed a 41% reduction in the chance of clinical pregnancy (adjusted Odds ratio = 0.59) for women with stage III-IV endometriosis and basal serum testosterone levels below 0.305 ng/mL undergoing IVF / ICSI treatment.

Next, the data was reanalysed and grouped according to women with basal serum testosterone below and above 0.305 ng/mL. No statistically significant differences were found between the 2 groups other than initial (234 vs 216 IU) and total dose (2689 vs 2511 IU) of gonadotrophins, along with HMG (854 vs 641 IU) was higher among the group of women with basal serum testosterone < 0.305 ng/mL.

Reproductive outcomes was then analysed similarly according to basal serum testosterone grouping. Interestingly, implantation rate (32.7% vs 24.1%), clinical pregnancy rate (48.9% vs 34.5%) and live birth rate (42.1% vs 31.0%) was significantly higher for women with basal serum testosterone levels above 0.305 ng/mL. On the other hand rates of miscarriage, preterm and multiple pregnancy were similar between the two groups (P > 0.2).

Overall, women with lower basal serum testosterone levels required higher initial and total doses of gonadotropins to achieve a similar ovarian response. The mechanism by which reduced testosterone levels adversely impacts IVF outcomes in women with endometriosis requires further study.


SUMMARY: DOES TESTOSTERONE AFFECT ENDOMETRIOSIS

Low levels of basal serum testosterone (< 0.305 ng/mL) among women with stage III-IV endometriosis, significantly reduces the chance of clinical pregnancy by 41% (adj odds ratio = 0.59), in the very first IVF/ICSI cycle, leading to a significant reduction of live birth rates (42.1% to 31.0%).


Limitations

  1. Retrospective study
  2. Other adrenal androgens and testosterone levels not measured


Similar studies

Gibson D A, et al. (2018). Dehydroepiandrosterone enhances decidualization in women of advanced reproductive age. https://doi.org/10.1016/j.fertnstert.2017.12.024

Gibson D A, et al. (2018). Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders. https://doi.org/10.3390/ijms19103276

Ono Y J, et al. (2014). A Low-Testosterone State Associated with Endometrioma Leads to the Apoptosis of Granulosa Cells. https://doi.org/10.1371/journal.pone.0115618

Pellicer A, et al. (1998). The Follicular Endocrine Environment in Stimulated Cycles of Women with Endometriosis: Steroid Levels and Embryo Quality. https://doi.org/10.1016/S0015-0282(98)00085-5


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