Mild stimulated cycles with timed intercourse in women with idiopathic infertility and decreased ovarian reserve: can it be a therapeutic option before oocyte donation?

Woman natural fertility declines physiologically with age, driven by accelerated follicular depletion and subtle ovulatory dysfunctions. As age at first pregnancy increases, women with decreased ovarian reserve (DOR) represent a growing proportion of those seeking assisted reproductive technology (ART). In vitro fertilization (IVF) outcomes in this population are often limited, leading to early referral for oocyte donation. However, the effectiveness of mild stimulated cycles with timed intercourse remains underexplored. This retrospective single-center study included all mild gonadotropin-stimulated cycles performed between January 1, 2000, and December 31, 2022, in women aged 18–42 years with DOR, defined as antral follicle count (AFC) < 8 and/or anti-Müllerian hormone (AMH) < 1.2 ng/ml. All women had regular cycles (≤ 26 or 27–35 days). A total of 643 cycles in 242 women were analyzed. Logistic regression identified predictors of clinical pregnancy and live birth per woman and per cycle. Median age at stimulation start was 39.1 years (IQR: 36.1–40.9), with median AMH 0.5 ng/ml (IQR: 0.3–0.9) and median AFC 6 (IQR: 4–8). The median number of cycles per woman was 2 (IQR: 1–4). The clinical pregnancy rate per woman was 22.3% (54/242), and 16.5% achieved at least one live birth (40/242). Age over 40 years (adjusted OR [aOR] = 0.44; 95% CI [0.25–0.78]; p = 0.01) and primary infertility (aOR = 0.65; 95% CI [0.45–0.96]; p = 0.03) were negatively associated with live birth. Conversely, the presence of more than one large or intermediate follicle at trigger was positively associated with live birth (OR = 1.47 and 1.58, respectively; p < 0.05). Mild gonadotropin stimulation with timed intercourse may represent a valuable therapeutic option for women with idiopathic infertility and DOR and should be discussed before considering oocyte donation. These findings support further prospective studies.