Recurrent Pregnancy Loss

William H. Kutteh, M.D., Ph.D.

Recurrent pregnancy loss is a profound personal tragedy to couples seeking parenthood and a formidable clinical challenge to their physicians. Although spontaneous abortion occurs in approximately 15 to 20% of clinically diagnosed pregnancies of reproductive-aged women, recurrent pregnancy loss occurs in approximately 1 to 2% of this same population.[1] Great strides have been made in characterizing the incidence and diversity of this heterogeneous disorder, and a definite cause of pregnancy loss can be established in approximately two thirds of couples after a thorough evaluation.[2] A complete evaluation will include investigations into genetic, endocrinologic, anatomic, immunologic, microbiologic, thrombophilic, and iatrogenic causes (Table [1]). The occurrence of recurrent pregnancy losses may induce significant emotional distress and in some cases intensive supportive care may be necessary. Successful outcomes will occur in more than two thirds of all couples.[3]

Table 1 Standard Evaluation and Management of Recurrent Early Pregnancy Loss Factor Diagnostic Evaluation Abnormal Result Therapy Genetic Cytogenetic analysis of both partners 3-5% Genetic counseling; donor gametes, PGD? Anatomic Hysteroscopy, hysterosalpingogram, or sonohysterography 15-20% Hysteroscopic septum resection, lysis of adhesions, hysteroscopic myomectomy Endocrinologic Endometrial biopsy or midluteal progesterone, TSH, prolactin, fasting insulin and glucose 8-12% Progesterone, levothyroxine, bromocriptine, cabergoline, metformin Immunologic Lupus anticoagulant, anticardiolipin antibodies, embryotoxicity assay? Immunophenotyping? 15-20% Acetylsalicylic acid, heparin, IVIG? Microbiologic Endometrial biopsy, cervical and vaginal cultures? 5-10% Antibiotics Thrombophilic Factor V Leiden, antithrombin? Protein C? Protein S? Prothrombin gene mutation, fasting homocysteine 8-12%? Heparin? Folic acid Psychological Mental status evaluation Varies Support group, counseling, psychiatrist Iatrogenic Review tobacco, alcohol and caffeine use; review exposure to toxins, chemicals 5% Eliminate consumption or exposure PGD, prostaglandin D; TSH, thyroid-stimulating hormone; IVIG, intravenous immunoglobulin.

The traditional definition of recurrent pregnancy loss included those couples with three or more spontaneous, consecutive pregnancy losses. Ectopic and molar pregnancies are not typically included. It is not clear whether occult early miscarriages diagnosed by sensitive human chorionic gonadotrophin assays should be included in these definitions. Several studies recently have indicated that the risk of recurrent miscarriage after two successive losses is similar to the risk of miscarriage in women after three successive losses; thus, it is reasonable to start an evaluation after two or more consecutive spontaneous miscarriages to determine the etiology of the pregnancy loss, especially when the woman is older than 35 years of age, or when the couple has had difficulty conceiving.[3] [4]

Miscarriages are considered any loss before 20 gestational weeks. Some authors further divide these into embryonic losses, which occur before the 9th gestational week, and fetal losses, which occur at or after the 9th gestational week to 20 weeks, although there is no developmental phase to justify this distinction. Those couples with primary recurrent loss have never had a previous viable infant, whereas those with secondary recurrent loss have delivered a pregnancy beyond 20 weeks previously and then suffered subsequent losses. Other investigators advocate the designation of tertiary recurrent loss to identify those women who have multiple miscarriages interspersed with normal pregnancies.

This issue of Seminars in Reproductive Medicine includes reviews on the research methodology relevant to recurrent pregnancy loss. Entire chapters are dedicated to genetic, anatomic, endocrinologic, immunologic, and thrombophilic associations with recurrent loss. The authors have devoted considerable effort to provide up-to-date information in each area and their efforts are greatly appreciated.

REFERENCES

• 1 Kutteh W H. Recurrent pregnancy loss. In: Precis An Update in Obstetrics and Gynecology. Washington, DC; American College of Obstetrics and Gynecology 2002: 151-161
• 2 Stephenson M D. Frequency of factors associated with habitual abortion in 197 couples.  Fertil Steril. 1996;  66(1) 24-29
• 3 Branch D W, Silver R M. Antiphospholipid syndrome.  ACOG Educ Bull. 1998;  244 302-3111
• 4 Carson S A, Branch D W. Management of early recurrent pregnancy loss.  ACOG Educ Bull. 2001;  24 1-12