Consider Anti-Ovarian Antibody Testing for ART: a Parameter to Improve the Success Rate of Your Clinic!

Review Article

Austin J In Vitro Fertili. 2015; 2(3): 1022.

Consider Anti-Ovarian Antibody Testing for ART: a Parameter to Improve the Success Rate of Your Clinic!

Eusebio S Pires*

Department of Obstetrics and Gynecology, University of Virginia, USA

*Corresponding author: Eusebio S Pires, Department of Obstetrics and Gynecology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA

Received: September 04, 2015; Accepted: September 21, 2015; Published: September 23, 2015


There is a steady and continuing trend towards later childbearing in developed countries, to some extent in developing countries and at the same time several infertile couples seek for Assisted Reproduction Techniques (ART) to conceive. ART has been used in the United States since 1981 to help women become pregnant however; the decision to undergo this expensive and time-consuming treatment can be difficult. ART can also alleviate the burden of infertility on individuals and families. With a chance of helping women get pregnant through IVF; there also are numerous hurdles that come along the way for a successful IVF, such as female age, embryo quality, ovarian response, poor implantation, poor diet and lifestyle. Usually ignored but, a new addition to this list could be the detection of serum Anti-Ovarian Antibodies (AOA) which have been demonstrated to further reduce IVF success rates. This review highlights recent research findings supporting AOA testing in women enrolled for ART prior to initiating them into the IVF program. In doing so it could help these women at the time of counseling, to give them a better perspective of a chance on how to improve their reproductive outcome. This simple counseling which involving a blood work done for testing serum AOA would not only ensure effectiveness of IVF, but also save on the time invested by the treating clinician and the monetary investment done by the patients and thus aim towards restoring fertility.

Keywords: Anti-ovarian antibodies; Ovarian autoimmunity; Infertility in women; IVF successes


Infertile couples, by the time they begin In Vitro Fertilization (IVF) treatment, are often desperate for children having been through years of intrusive investigations. Since the birth of Louise Brown, innovations in Assisted Reproductive Techniques (ART) have overcome numerous seemingly undefeatable barriers to allow couples the chance to have babies. Significant developments in the first decade led to greater efficiency and expanded accessibility of IVF to the general public. Efforts continue to focus on potential ways to increase the success of ART using Preimplantation Genetic Diagnosis (PGD) for aneuploidy screening [1]. Of all, improving the efficiency of cryopreservation of oocytes and of ovarian tissue transplantation promises to provide options to modern day women. Despite these major technological advances achieved by ART in the last three decades, intense efforts to follow the long term impact of these technologies have to be undertaken knowing the fact that the fruit of this technology- child conceived with IVF is currently around 33 years of age. Furthermore, many technologies such as ICSI, in vitro maturation, oocyte cryopreservation and vitrification, and PGD have limited research findings on developmental outcomes. Heightened awareness of potential health risks secondary to ovulation inducing medications, in vitro culture conditions, and oocyte/embryo manipulations is paramount to the continuous surveillance of rare complications of ART that may only manifest over time. Some of the known key factors with IVF success rates [2]:

1. Age and IVF. The younger the woman, the higher the IVF success rates. Higher risk for miscarriage, especially after age 40.

2. Type of fertility problem. Recurrent miscarriage, infertility in both the male and female, uterine abnormalities, blocked or absent tubes, ovarian dysfunction, or low sperm quality and motility can result in lower IVF success rates.

3. Lifestyle habits. Women with a history of Sexually Transmitted Diseases (STDs) and Pelvic Inflammatory Disease (PID) may have lower IVF success rates.

4. The fertility center data. At the time of an interview with the treating clinician, it is a good practice to ask for the success rates and stories from the IVF lab where the patient plans to register. This rate varies from clinic to clinic.

Autoimmunity of the reproductive system

Ovarian autoimmunity: Apart from the factors discussed above, there is one factor that has not been given substantial consideration while enrolling a candidate for IVF- ‘Ovarian Autoimmunity’. Like all other organs the reproductive tissue also undergoes an autoimmune attack. Although many researchers have enormously contributed towards this field, till date there have been several agreements and differences in opinions. Among the sexes, females are generally more prone to have autoimmune diseases than males. In most endocrine autoimmune diseases, an abnormal level of the regulatory hormone is a primary diagnostic indicator of potential pathology. The diagnosis is confirmed by measurement of specific autoantibodies. Regardless of the mechanisms involved in autoimmune pathology, detection of specific autoantibodies remains the most practical clinical and research marker of autoimmune disease [3]. The relation between regulatory hormones and ovarian autoimmunity is more complex than that of noncyclic endocrine organs. Ovarian function is cyclic and regulated by cyclic changes in gonadotropin levels. During normal function, hormone levels vary, and during the process of ovarian aging associated with menopause, changes are erratic [4]. For example a single measurement of FSH may not be a reliable indicator of ovarian function. Autoimmune and non autoimmune ovarian failures are not readily differentiated by endocrine profiles. The presence of autoantibodies in individuals without end-organ dysfunction is associated with a higher risk for development of autoimmune disease. Ovarian antibodies have been shown to be present in infertile women although showing normal levels of FSH and inhibin-B, suggesting that ovarian antibodies are independent predictors of potential autoimmune ovarian failure [5].

Pathological role of ovarian antibodies: Presence of these antibodies to various cellular components of the ovary can (a) reduce fertilization rates (b) decrease pregnancy rates (c) generate a poor response to gonadotropin stimulation (d) affect egg and embryo development (e) could be responsible for implantation failures [6].

Selection of subjects

There are additional confounding factors in studies involving infertility and ovarian autoimmunity. A potential source of variability is related to differences in treatment history. Cross-sectional study designs are common in infertility. In Vitro Fertilization and Embryo Transfer (IVF-ET) has become a promising treatment for infertility with various underlying causes.

Presence of serum Anti Ovarian Antibodies (AOA) in general circulation of women registered for the IVF-ET program [7-11] has been shown using Enzyme Linked Immunosorbent Assay (ELISA) and Indirect Immunofluorescence (IIF). These AOA do not necessarily appear after follicular aspiration as pre-existing AOA levels have been reported in some studies. In some of these patients an increase in AOA is seen with an increase number of IVF attempts [8]. As the likelihood of pregnancy changes with succeeding cycles, variable treatment history may confound the study result. A question has been raised about possible effects of IVF treatment on the prevalence of ovarian antibodies [8,12,13] and zona pellucida antibodies [14]. It is also possible that individuals with ovarian antibodies have repeated treatment failure and thus undergo multiple treatment cycles [15].

Few studies have assessed women before infertility treatment. The question of treatment effects is not resolved but is a consideration in study design. A major difference among studies is the extreme variation in inclusion and exclusion criteria for infertility study and control groups. Study groups may be defined by diagnostic category, follicular phase FSH, or functional outcomes, such as fertilization, gonadotropin responsiveness, or pregnancy. In addition, comparison/ control groups may include tubal factor, male factor, or normally cycling women. In couples initially classified as “male factor” infertility, the woman may be a poor responder to gonadotropin stimulation and have ovarian antibodies.

Clearly, it is difficult to compare studies with such diverse study groups. Furthermore, use of an infertility subgroup as a control group in which the possibility of ovarian autoimmunity has not been eliminated may confound identification of autoimmunity in the study group. It has been reported that ovarian autoimmunity is primarily associated with unexplained infertility, but this does not rule out ovarian autoimmunity associated with other diagnostic classifications, as women may have more than one etiologic condition contributing to infertility [13].

Autoimmunity and IVF

The hypothesis of an underlying autoimmune mechanism has been reported in some cases of repeated, unexplained IVF failure where the presence of AOA has been described [16], particularly in Premature Ovarian Failures (POF) / Primary Ovarian Insufficiency (POI) [17] and after follicular puncture for IVF [18,5]. An earlier study demonstrated a negative correlation between AOA levels in serum samples from IVF patients, the number of oocytes collected, the number of embryos obtained and the pregnancy rate [18]. Subsequently, these results have been confirmed in several other studies [12]. It has been demonstrated in some cases that AOA appear after follicular aspiration while in other cases, pre-existing AOA levels have been shown to increase with the number of IVF attempts [8].

Specific ovarian antigens still remain to be clearly delineated in human ovarian autoimmunity. It is possible that several different target antigens are involved in ovarian autoimmunity [6,10,11,19-21]. The auto antigens identified till date demonstrates the pathological role of AOA, and have been proposed to be involved in human ovarian autoimmunity. These target proteins differ in terms of their molecular identities and cellular localizations respectively. As there is evidence for both oocyte and cellular antigens in ovarian autoimmunity, it is likely that the best predictive value will be obtained with detection of antibodies to multiple antigens. In Figure 1 it has been demonstrated that sera having AOA immunoreactive to various compartments of the ovary. Although the oocyte seems the primary target, the other somatic cells of the ovary are also attacked. The specificity of assays detecting AOA has been questioned [22] and a simple sensitive test was reported to overcome this problem [9].