Case: A 34-year-old G0 patient presented for initial consultation after 3 consecutive IVF cycle failures at another regional IVF center. The indication for IVF was a severe case of male infertility, with less than 5 million total sperm. The patient produced good oocyte numbers in all 3 IVF cycles (n=8-12), with a majority being mature. Good fertilization (>60%) was accomplished in all cycles, utilizing intracytoplasmic sperm injection (ICSI), and a total of 10 blastocyst stage embryos (4, 3 and 3) were cryopreserved after trophectoderm biopsy for PGS. In each of the 3 IVF cycles, No euploid (chromosormally normal) embryos were identified after PGS. The patient, therefore, had no embryo transfer in any of her cycles. She, however, had 9 allegedly chromosomally abnormal, and 1 embryo that failed to give a reading result, cryopreserved.
She presented to CHR with the principal question whether her cryopreserved, allegedly “aneuploid,” embryos could be transferred at CHR since the IVF center where those embryos had been generated refused to do so.
Review of her medical record further revealed a BMI of 24, an FSH of 8.6mIU/mL and an AMH of 1.1ng/mL. Her testosterone levels were in normal midrange but her SHBG was mildly elevated at 128nmol/L. All remaining labs were within normal ranges. Among her 9 cryopreserved “aneuploid” embryos, 3 were chaotic, 4 monosomic and 2 trisomic (likely lethal).
Analysis: This was a young woman, presumed to demonstrate infertility due to a severe male factor. She, however, demonstrates mildly elevated age-specific FSH and mildly low age-specific AMH and, therefore, also carried a diagnosis of mild premature ovarian aging (POA), also called occult primary ovarian insufficiency (oPOI). Though her testosterone levels were in range, her relatively high SHBG suggested that, considering her hormone receptor memory, they actually may have been a little low. Male infertility remained the most likely primary cause of this couple’s infertility. We, however, felt that her POA/oPOI could also contribute to the couple’s infertility by negatively affecting egg quality.
The couple was advised that under an experimental consent protocol CHR would feel comfortable transferring her 4 monosomic, 2 trisomic and 1 undetermined embryos. We recommended against transfer of the 3 chaotic embryos because in our center’s preliminary experience, we failed to establish pregnancies. In contrast, transfers of monosomic and trisomic embryos resulted in chromosomally normal pregnancies in almost 50% of transfers. We also discussed with the couple whether to transfer their aneuploid embryos or keep them frozen for future potential use, and the decision was to proceed with another fresh IVF cycle.
Resolution: Since the couple was desirous of 3 or more children, they decided to keep their cryopreserved allegedly “aneuploid” embryos “on reserve,” and to pursue another fresh IVF cycle. The female, therefore, was pre-supplemented with DHEA and CoQ10, following the center’s standard protocol for women with POA. As expected, her SHBG under DHEA supplementation declined to 69.0 nmol/L, confirming our suspicion that she, likely, had been mildly hypo-androgenic despite apparently normal testosterone levels.
In a subsequent IVF cycle, she produced a record 14 oocytes, of which 9 fertilized and 6 reached day-3. Two embryos were transferred on day-3 without PGS, and the patient conceived a singleton pregnancy, resulting in a normal vaginal delivery at term. The couple currently still has 4 day-3 embryos cryopreserved from their most recent cycle at CHR plus 10 blastocyst stage embryos from 3 prior PGS cycles elsewhere.
Conclusions: This case illustrates a few often-overlooked facts: (i) Even when an obvious cause of infertility is identified, a second significant cause may co-exist. (ii) FSH and AMH levels must be assessed in age-specific fashion if women with mild POA are to be correctly diagnosed. (iii) Women with POA, likely, will conceive quicker with day-3 than with days-5/6 transfers. (iv) Currently PGS, in CHR’s opinion, is unable to determine accurately whether an embryo is chromosomally normal or not. PGS should, therefore, be avoided.
This is a part of the April 2017 CHR VOICE.