A 34-year-old female who never before had conceived presented for a third opinion consultation because of bilateral endometriomas. She was single and used oral contraceptives for the last 6 years. Her past medical history was insignificant, except over the last 18 months for increasing dysmenorrhea and, with deep penetration, dyspareunia.
Her gynecologist suspected that she suffered from endometriosis and had recommended a laparoscopy over a year earlier but the patient decided against having the surgery. On her last annual examination by the gynecologist, ca. two weeks prior to presentation, she palpated an enlarged ovary on her left. A subsequent ultrasound revealed bilaterally endometriomas, with the left ovary being significantly larger than the right. Her gynecologist referred her for surgery to a gynecological surgeon, practicing robotic surgery. Both agreed that she should have surgery.
She now presented to CHR for a third opinion.
A repeat pelvic ultrasound confirmed bilateral endometriomas, with the left ovary seeded by at least two distinct endometriomas of ca. 3x3x3cm and2x2x2cm. Her right ovary contained a single ovary of ca. 3cm diameter. Both ovaries looked mildly polycystic but were, otherwise, normal. Her FSH was 8.4mIU, while her AMH was 2.1ng/mL.
The patient also revealed a positive ANA (speckled) and positive anti-phospholipid antibodies (APAs) in IgG and IgM.
Since the patient was desirous of future fertility and was nulliparous, she was advised against surgery since surgery, likely, would negatively affect her functional ovarian reserve (FOR), which at that point still appeared to be in normal range. Regular follow up evaluations with ultrasound every 6 months were recommended to assess potential growth of her endometriomas and she was advised of rupture risk and related symptoms. Finally, she was also advised to start taking a bASA daily to counteract potential thrombotic risks due to APAs.
This patient returned 2 years later, now 36 years old. She had undergone robotic surgery ca. 3 months after her initial presentation to CHR, and was advised that “the surgery had gone very well, with no normal ovarian tissue lost.” After she had gotten engaged, she had stopped OCPs approximately 1 year earlier but had not conceived since. In addition, her periods were irregular since stopping OCPs. Her gynecologist had performed baseline testing ca. 2 weeks prior to presentation: FSH was 12.8 mIU /mL and AMH was 0.4ng/mL.
This patient in 2 years had gone from normal FOR to obviously low ovarian reserve. Though our strong suspicion was that the surgery at least contributed to this development, hypothetically she could have developed low FOR also simply via natural progression of her endometriosis. She, now, however suffered from clear premature ovarian aging (POA), also called occult primary ovarian insufficiency (oPOI). Considering her young age, this patient required quick treatment since we could not exclude the possibility that her ovarian reserve was very quickly spontaneously declining.
The patient underwent an updated complete revaluation: She still demonstrated a positive ANA and APAs but now also IgG, IgM and IgE gammopathies (all high). She, thus, very clearly demonstrated evidence of immune system hyperactivity and, therefore, potentially increased miscarriage risk. Moreover, she demonstrated low testosterone (and other androgens) and mildly elevated SHBG. She therefore, according to CHR’s protocol for women with low FOR, was pre-supplemented with dehydroepiandrosterone (DHEA) and CoQ10 for approximately 6 weeks prior to IVF start. Because of her still young age, she was stimulated in a microdose agonist protocol with maximal stimulation dosages. She conceived and delivered following her 3rd cycle attempt.
Her pregnancy was complicated by preeclampsia, starting at 28 weeks. She was delivered by Cesarean section at 30.5 weeks of an only 2-pound infant, who required no intubation. Mother and baby did well.
Lessons to be learned
1) Never operate on ovarian endometriomas in women who are still desirous of pregnancy, unless a medical emergency is the reason (ovarian torsion or rupture of an endometrioma). And, even then, perform surgery as conservatively as possible to avoid as much as possible resection of healthy ovarian tissue.
2) Remember the statistical association of endometriosis with autoimmunity and the association of autoimmunity with miscarriage risk and pregnancy complications, like preeclampsia, small for gestational age infants and premature delivery.
This is a part of the September 2017 CHR VOICE.