The third approach is to use donor eggs or sperm. This treatment is particularly useful for patients with parental genetic factors and recurrent pregnancy loss, for example, a patient with Robertsonian translocations involving homologous chromosomes. In these patients, their genetic anomaly always results in unbalanced gametes, and the use of donor oocyte or donor sperm is recommended. Use of donor gametes among patients with a history of recurrent pregnancy loss can be useful in other cases where couples are at higher risk for unbalanced offspring because of carrying other forms of chromosomal rearrangements, such as reciprocal translocations or advanced maternal age. In these cases use of donor gametes was demonstrated to be as effective as its use in matched patients without such a history (358). In all cases of balanced translocations or embryonic aneuploidy, genetic counseling is recommended.
Anatomic Anomalies Hysteroscopic resection represents state-of-the-art therapy for submucous leiomyomas, intrauterine adhesions, and intrauterine septa. This approach appears to limit postoperative sequelae while maintaining efficacy in terms of reproductive outcome (72,76,77,358– 362). Use may be safely extended to patients with DES exposure, hypoplastic uteri, and complicated septal anomalies (76,77,363). Attempts to improve on standard hysteroscopic metroplasty, which is typically performed in the operating room using general anesthesia, often with laparoscopic guidance, are under investigation. Ultrasonographically guided transcervical metroplasty is reported to be safe and effective (359). Ambulatory, office-based procedures, including septum resection under ﬂuoroscopic guidance, are attractive options (360).
For patients with a history of loss secondary to cervical incompetence, placement of a cervical cerclage is indicated. This is usually performed early in the second trimester after documentation of fetal viability. Cervical cerclage should be considered as a primary intervention for women with DES-associated uterine anomalies.
Some investigators have proposed the use of ovulation induction for the treatment of recurrent pregnancy loss (361,362). The theory behind its use in these patients rests on hypotheses that ovulation induction is associated with healthier oocytes. Healthier oocytes, in turn, may decrease the incidence of luteal phase insufficiency, which should result in improved pregnancy maintenance. This approach grossly oversimplifies the mechanisms involved in implantation and early pregnancy maintenance. Until appropriately studied, use of empiric ovulation induction for treatment of unexplained recurrent pregnancy loss should be viewed with caution. Evidence from small studies indicates such use is not effective (361). Still, use of ovulation induction in some subsets of patients with recurrent pregnancy loss could be of benefit. For instance, stimulating folliculogenesis with ovulation induction or luteal phase support with progesterone should be considered for women with luteal phase insufficiency. The efficacy of these therapies, however, is not substantiated (363). Ovulation induction might also be beneficial for women with hyper-androgen and LH hypersecretion disorders, especially following pituitary desensitization with gonadotropin-releasing hormone agonist therapy (112). This treatment remains controversial because the only large, prospective, randomized controlled trial to date reports no therapeutic efficacy; none for prepregnancy pituitary suppression nor for luteal phase progesterone supplementation (364).