Shifting Paradigms in Diminished Ovarian Reserve and Advanced Reproductive Age in Assisted Reproduction: Customization Instead of Conformity

Abstract

As women are increasingly delaying childbearing into their 30s and beyond, diminished ovarian reserve (DOR) and advanced reproductive age (ARA) patients are bound to become a large proportion of all assisted reproductive technology practices. Traditional controlled ovarian stimulation (COS) protocols for DOR and/or ARA have had some limited success, but pregnancy rates are lower and cycle cancellation rates are higher than their younger counterparts with normal ovarian reserve. Though many physicians have a selection of favorite standard protocols that they use, patients with DOR may require closer monitoring and customization of the treatment cycle to address the common problems that come with low ovarian reserve. Frequent issues that surface in women with DOR and/or ARA include poor follicular response, premature luteinizing hormone surge, and poor embryo quality. Limited published evidence exists to guide treatment for DOR. However, use of minimal or mild doses of gonadotropins, avoidance of severe pituitary suppression, and consideration for luteal phase stimulation and a "freeze all" approach are possible customized treatment options that can be considered for such patients who have failed more traditional COS protocols.

Luteal-phase ovarian stimulation increases the number of mature oocytes in older women with severe diminished ovarian reserve

“…In these situations, there are usually no oocytes retrieved despite apparently normally growing ovarian follicles with adequate estradiol (E2) concentrations using meticulous repeated follicular aspiration and flushing (Kumaran et al 2015). Patients with poor prognosis also tend to have high cancellation rates, along with lower pregnancy and live birth rates (Reed et al 2015). Thus, more research has gone into the mechanisms of follicular growth and how clinicians can better manipulate the natural female cycle in order to yield better results for women with poorer response to treatments.…”

Use of Clomiphene Citrate in minimal stimulation in vitro fertilization negatively impacts endometrial thickness: an argument for a freezeall approach

“…Instead, estrogen priming was performed to allow for follicular synchronization prior to the stimulation. For minimal stimulation IVF ( Figure 1 ), clomiphene citrate 100mg was given orally for 10 days starting on menstrual cycle day 2-3 ( Reed et al ., 2015 ).One hundred fifty international units (IU) of human menopausal gonadotropin (HMG) were added for days 5, 7, and 9. For mild stimulation, patients were on recombinant FSH 150 IU daily.…”

“…In addition, the lower dose of gonadotropin used may allow for better quality oocytes and embryos ( Baart et al ., 2007 ; Haas et al ., 2015 ). We offer the minimal stimulation approach to patients with expected poor ovarian response mainly due to diminished ovarian reserve and/or advanced reproductive age with a plan for embryo accumulation and subsequent frozen embryo transfer (FET) ( Reed et al ., 2015 ). A commonly prescribed minimal ovarian stimulation protocol uses daily clomiphene citrate (CC) and a small amount of gonadotropin on days 5, 7, and 9 of the ovarian stimulation ( Figure 1 ) ( Reed et al ., 2015 ).…”

Effect of Yushen zhuyun decoction on rats with diminished ovarian reserve induced by tripterygium glycosides

“…Currently, it is reported that in vitro fertilization and embryo transfer (IVF-ET) could improve the pregnancy rate of husband and wife with infertility; however, the pregnancy rate is still less than 50% [3,4]. The reasons for infertility are complex, and the diminished ovarian reserve (DOR) is one of the most important reasons [5,6]. Ovarian reserve (OR) is defined as the number and quality of remaining oocytes in ovarian cortex, reflects the fertility potency and reproductive endocrine function of women [7,8].…”