Journal of Assisted Reproduction and Genetics, Vol. 12, No. 4, 1995 CLINICAL ASSISTED REPRODUCTION Involvement of Ovarian Factors Magnified by Pharmacological Induction of Multiple Follicular Development (MFD) in the Increase in Ca125 Occur During the Luteal Phase and the First 12 Weeks of Induced Pregnancies A N N A MARIA PAOLETTI, 1 GIAN GIACOMO SERRA, 1 VALERIO MAIS, 1 SILVIA AJOSSA, 1 STEFANO GU ER R I ERO, 1 MARISA ORRI), 1 and GIAN B E N E D E T T O MELIS 1'2 Submitted: January 16, 1995 Accepted: March 13, 1995 Objective: To evaluate the relationship o f ovarian activity on Ca125 production, we studied whether Ca125 produc- tion varies during the menstrual "cycle both in normal ovulatory women and in womenwhose ovarian factors are significantly stimulated by multiple follicular devel- opment (MFD). Furthermore, since the first 12 weeks o f pregnancy is characterized by the enhancement o f corpus luteum function mainly in MFD-induced pregnancies, Ca125 levels were also evaluated in the first quarter o f pregnancy both in spontaneous and in MFD-induced pregnancies. Subjects: Subjects were normal ovulatory women in the late follicular phase (FP) (N = 20) and in the luteal phase (LP) (N = 20), 32 infertile women submitted to MFD with pure FSH, and 40 pregnant women in which pregnancy occurred spontaneously (N = 20) or after induction of MFD (N = 20). Results and Conclusions: In regularly cycling women plasma Ca125 levels were constant during the menstrual cycle. In contrast, in stimulated cycles Ca125 levels were significantly higher (P < 0.0008) in the LP than in the FP. In addition, in these subjects Ca125 levels in the LP were significantly correlated (P < 0.0001, r = 0.686) with E 2 plasma levels. These data strongly suggest that an in- crease in corpus luteum functioncould be involved in Ca125 production. Since granulosa cells have not been demonstrated to produce Ca125, it can be hypothesized i Istituto di Ginecologia Ostetricia e Fisiopatologia della Riproduzione Umana, Ospedale San Giovanni di Dio, Via Ospedate 46, 09124 Cagliari, Italy. 2 To whom correspondence should be addressed. that endometrial or peritoneal cells submitted to exagger- ated stimulation by ovarian activity are the source o f in- creased Ca125 secretion. In agreement with this hypoth- esis, Ca125 levels were significantly higher in the first weeks o f spontaneous pregnancies than in the luteal phase and they were also higher in MFD-induced preg- nancies than in spontaneous pregnancies (P < 0.001). KEY WORDS: Ca125; progesterone; estradiol; corpus luteum; multiple follicular development. INTRODUCTION Ca125 is a glycoproteic surface antigen expressed in the organsderiving from coelomic epithelium. Its identification resulted from binding with the murine monoclonal antibody OC-125, which recognizes an antigenic determinant, originally associated with ovarian serous cystoadenocarcinoma (1). Elevated levels of Ca125 can be found in women with ovarian cancer (2) and in patients with other gynecological (3) and nongynecological malignancies (4). Mainly in ovarian cancer a direct relationship is commonly found between Ca125 levels and tumor cell replica- tion, representing the major marker to evaluate the progression of the disease (2). Ca125 is also ex- pressed in gynecological and nongynecological be- nign conditions, such as endometriosis (5), uterine myomas (6), ovarian cysts (7), and pelvic inflamma- tory disease (8). Nevertheless, only a slight increase in Ca125 often characterizes these conditions. Very low concentrations of Ca125 are usually de- 263 1058-0468/95/0400-0263507.50/0 9 1995 Plenum Publishing Corporation