The aim of this trial is to examine the possible effects of hCG administration for eight weeks prior to IVF/ICSI in women with low ovarian reserve. Primary outcome is the proportion of the antral follicle count that reach the pre-ovulatory stage.

One of the fundamental goals in In Vitro Fertilisation (IVF) is obtaining a high number of good quality oocytes, in order to select and transfer embryos with the highest possible implantation potential thereby optimizing the chance of a pregnancy and ultimately a live birth. This is done by applying an individualized controlled ovarian stimulation (iCOS) protocol, primarily based on ovarian reserve markers like antral follicle count (AFC) and Anti-Müllerian hormone (AMH), when deciding the follicle stimulating hormone (FSH) stimulation dose. Certain patients, the so called "poor ovarian responders' (PORs), pose a clinical challenge because they have a poor ovarian reserve and develop a limited number of pre-ovulatory follicles in respond to ovarian stimulation despite high FSH stimulation doses, thus experiencing reduced live birth rates.

The aim of the present study is to examine the possible effects of long-term LH activity by the administration of hCG for eight weeks in between two identical IVF/ICSI cycles and compare cycle characteristics and outcome. The primary outcome is the follicular output rate (FORT) which reflects the proportion of antral follicles at the start of controlled ovarian stimulation that reaches the pre-ovulatory state. Secondary outcomes include amongst others AMH and antral follicle count at baseline (cd 2-3), number of pre-ovulatory follicles, oocytes retrieved, and embryos developed.

We hypothesize that eight weeks of androgen priming by hCG increases the proportion of antral follicles that reaches the pre-ovulatory state during controlled ovarian stimulation for IVF/ICSI in women with poor ovarian reserve.

Inclusion Criteria:

• Regular menstrual cycle (23-35 days)
• 1.-5. IVF/ICSI cycle at inclusion
• AMH < 6.29 pmol/L (Elecsys® AMH assay)

Exclusion Criteria:

• Uterine malformations or hydrosalpinx
• Submucosal uterine myomas
• Uterine polyps
• Allergy to standard IVF/ICSI medication
• Endometriosis stage III-IV
• Severe comorbidity
• Preimplantation genetic testing
• Testicular sperm aspiration/extraction
• Tumors in the hypothalamus or pituitary gland
• Active thromboembolic disease

On request, the study protocol and unidentifiable individual study data collected during the trial, including stored biobank samples, can be shared with research groups with relevant aims and a methodologically sound proposal. Approvals by necessary ethic committees and the Danish Data Protection Agency will be needed before sharing of data. All costs for data sharing will be covered by the party requesting the data. Data cannot be shared with groups working on research projects with the same aims, secondary aims or purposes. Furthermore, no data can be shared until 3 months after publication of first papers on the primary and secondary outcomes in this study. Biobank samples cannot be shared with research groups outside Denmark. Proposals of data sharing should be directed to anja.bisgaard.pinborg@regionh.dk. To gain access, data requestors will need to sign a data sharing agreement.