The follicular hormonal profile in low-responder patients undergoing unstimulated cycles: Is it hypoandrogenic?

STUDY QUESTION: What is the final hormonal milieu of pre-ovulatory follicles of low-responder (LR) patients undergoing unstimulated cycles? SUMMARY ANSWER: Neither androgen secretion nor LH was impaired in pre-ovulatory follicles of LR women. WHAT IS KNOWN ALREADY: Therapies currently used to improve ovarian response in LR women have an impact on the final hormonal follicular milieu, and these changes are believed to be partially responsible for determining the success rate in these women. Surprisingly, as far as we know, there is no report of the final hormonal profile of LR women undergoing unstimulated cycles or evidence that follicular androgen secretion in LR women is impaired. STUDY DESIGN, SIZE AND DURATION: A prospective case-control study including 94 women, 36 normal controls and 58 LR patients (19 Young ≤ 35 years LR and 39 Aged >35 years LR) from 2009 to 2011. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Fifty-eight LR women were divided into two groups: Young LR (age ≤ 35; n = 19) and Aged LR (ALR; age >35; n = 39). The control group (group C) comprised 36 egg donors undergoing an unstimulated cycle in our IVF unit. Serum and follicular fluid hormonal concentrations for estradiol (E2), progesterone, testosterone and androstendione were measured. The spindle parameters of metaphase II oocytes generated from these groups were also analysed. MAIN RESULTS AND THE ROLE OF CHANCE: Pre-ovulatory follicles from LR patients had similar androgenic and LH concentrations to those observed in the control group. However, higher intrafollicular concentrations of FSH and progesterone were observed in ALR. Moreover, no differences were found for the spindle evaluation of oocytes between groups by the Oosight technology. LIMITATIONS, REASONS FOR CAUTION: The controls were younger and had a lower BMI than the LR women. The sample size available restricted statistical power. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that the problem with LR women is not the final pre-ovulatory follicular androgen concentration since this is similar to normal responders, but in the ability to respond to controlled ovarian stimulation protocols. Therefore, efforts should be focused on long-interval androgen priming to potentially increase the recruitment of small antral follicles rather than increasing the intraovarian androgen levels within the current cycle. STUDY FUNDING/COMPETING INTEREST: The present project has been supported by the R+D programme from the Generalitat Valenciana (Regional Valencian Government) IMPIVA MIDTF/2010/95. The authors have no conflict of interest to declare.

Systemic methotrexate to treat ectopic pregnancy does not affect ovarian reserve.

OBJECTIVE: To evaluate whether methotrexate (MTX) compromises ovarian reserve and future reproductive outcome in women undergoing assisted reproductive technology (ART), when it is used as first-line treatment for ectopic pregnancy (EP). DESIGN: Prospective, observational study. SETTING: University-affiliated private IVF unit. PATIENT(S): Twenty-five women undergoing IVF-ICSI who were treated with MTX (1 mg/kg IM) for an EP after ART. INTERVENTION(S): Evaluation of reproductive outcome and serum anti-Müllerian hormone (AMH) levels. Serum AMH was evaluated before administering MTX and >or=1 week after the resolution of the EP. Reproductive outcome was evaluated by comparing subsequent IVF-ICSI cycles after EP resolution. MAIN OUTCOME MEASURE(S): Serum AMH levels, cycle length, gonadotropin dose required, peak serum E(2) level, oocytes collected, and embryos obtained. RESULT(S): Serum AMH levels before MTX were not statistically significantly different from those after treatment (3.7 +/- 0.3 ng/mL vs. 3.9 +/- 0.3 ng/mL). Patients undergoing a subsequent cycle after systemic treatment for EP had similar cycle durations (10.3 vs. 10.8 d), gonadotropin requirements (2,775 vs. 2,630.3 IU), peak E(2) levels (1,884.3 vs. 1,523.6 pg/mL), number of oocytes retrieved (12.1 vs. 10.5), and total number of embryos obtained (7.1 vs. 6.5). CONCLUSION(S): Single-dose MTX is a safe first-treatment choice that does not compromise future reproductive outcomes in women who are diagnosed with EP after ART.