Recurrent Spontaneous Abortions
Short Summary

38-year-old female suffers from endometriosis and repeated miscarriages. During a 2 years period, she underwent 2 spontaneous miscarriages, both at 7 weeks' gestation. Her investigation included normal anatomic (HSG/hysteroscopy), genetic, biochemical, hormonal and immunological (autoantibodies) testing. Her husband suffers from OTA and bacteriospermia, which was treated accordingly.

Patient's Questions
1)         What is the most probable cause of the two spontaneous abortions? What, if any, additional tests do you advise?
2)         To promote pregnancy and the correct evolution of the same, do you consider excision of the endometrial cysts of the right ovary advisable?
3)         What, if any, treatments and/or methods to you suggest?
4)         Can you indicate the centers of excellence in Italy and/or Europe for infertility treatment?
Medical Background

Patient's History
Couple with recurrent spontaneous abortion 
Endometriosis was found in 2001, which was always treated using estrogen-progestin therapy, specifically Mercilon and Tri-minulet.
In 2006, the patient was hospitalized for intense pain in the pelvic/abdominal area with a diagnosis at discharge of “hemorrhagic corpus luteum.”
The patient is a carrier of endometrial cysts affecting the right ovary as shown in the ultrasounds performed from 2006 to present.
Beginning in May 2007, the patient began trying to become pregnant, and after some time was still unsuccessful. In October 2007, therefore, the patient underwent hysterosalpingography which did not show any pathological conditions of the tubes.
First pregnancy in the same month, October 2007, which, however, ended with dilation and curettage for intrauterine abortion at the 7th week.
In November 2007, the patient’s husband underwent semen analysis, the results of which are attached, with findings favoring ”hypokinesia.”
In May 2008, a second pregnancy with the same development as the previous one: dilation and curettage in July 2008 for intrauterine abortion at the seventh week. Karyotype of the abortus was not possible as there was not enough matter. Histological examination was negative.
In July 2008, the patient underwent a series of diagnostic tests to verify the possible causes behind the prior abortions; among these exams are: blood tests with prolactin levels, autoantibodies, glucose tolerance test, thyroid function and cytogenetic analysis (relative results are attached).  
The patient has been under the care of Dr. X since October 2008, in whose study she underwent a pap-test, vaginal cultures and hysterogram.
The patient’s husband had a sperm culture done with evidence of enterococcus infection. At this time the semen analysis was repeated with evidence of "mild asthenospermia and moderate teratospermia” and observation of numerous areas of aggregated sperm.
Both were therefore treated for one month with a therapy of Bassado (doxycycline) for the first 15 days and Ciproxin (ciprofloxacin) for the remaining 15 days. The results of the patient’s blood tests were within normal limits (relative results are attached). The cytogenetic analysis of 07/2008 was also normal (see results).
The following were also performed on the patient's husband:
- color doppler ultrasound of the proximal seminal duct: normal results.
- ultrasound of the distal seminal duct with evidence of normal findings for prostate, ejaculatory ducts and vas deferens ampulla; diameter of the seminal vesicles at the high end of normal equal to 15 mm with internal sonolucent areas due to stasis, for which exam findings favor “vesicular congestion without inflammation in prostatic secretion.”
From November 2008 through February 2009, additional blood tests on the patient to check hormone levels, the results of which are attached.
In January 2009, the husband again underwent a sperm culture with evidence that the infection from enterococcus was eliminated. In addition, he had another semen analysis showing: “mild asthenospermia, moderate teratospermia” (see attachment).
 

Expert's Opinion

In summary, the patient suffers from endometriosis and repeated miscarriages, where the "most common" cause is chance. However, due to her age, I would investigate and treat her as patient with recurrent abortions (despite the fact that she underwent only 2 and not 3 miscarriages)
Before answering the question, there are several issues that I would like to clarify:
-       How was the diagnosis of endometriosis done (US or laparoscopy and biopsy)? 
-       Did the autoantibodies mentioned include: lupus anticoagulant, anticardiolipin and thrombophilic testing?
-       If the aforementioned tests are/ will be normal- so she would probably be classified as a patient with idiopathic repeated miscarriages, with a reasonable chance for future term pregnancy.
Regarding your questions:
  • Verify that the aforementioned tests were done/normal (lupus anticoagulant, anticardiolipin and thrombophilic testing)
  • The patient should start taking folic acid, 5 mg/ day and her husband should take any anti-oxidant preparation that includes coenzyme Q10 (30-60 mg/day).
  • Start treatment with timed IUI and luteal support which should include any vaginal micronized progesterone, mini-aspiring (75-100 mg/day) and hCG (2500 IU twice a week).
  • The addition of low molecular weight heparin (Clexan, 40 mg/day) or even IVIG, should be considered only in case of more miscarriages. Moreover, if another miscarriage will occur- send a specimen from the abortus to karyotyping.
  • If no pregnancy occurs after 2-3 cycle, proceed to COH (with gonadotropins) and IUI, with the same luteal support, except for hCG (that should be included only after pregnancy is diagnoses and when no risk of severe ovarian hyperstimulation is identified)
  • Regarding the endometrioma- if the diagnosis of endometriosis was done by laparoscopy/biopsy, I would justify a repeated laparoscopy and excision of the endometrioma only after 1-2 failed IVF cycle attempts (if will be required), and in the meantime observe. Otherwise, laparoscopy is justified.

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