Poor Ovarian Responders Undergoing IVF Using Luteal Ovarian Stimulation Versus Follicular Ovarian Stimulation

Study Overview
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Brief Summary
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The investigators attempted to compare the clinical outcomes and cumulus genes expression in poor ovarian responders undergoing luteal ovarian stimulation or follicular ovarian stimulation in in vitro fertilization cycles.

Detailed Description
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Multiple follicular wave theory proposed by Baerwald et al. implied that follicle recruitment may occur in the luteal phase of menstrual cycle. Therefore, luteal phase ovarian stimulation (LPOS) was considered as a potential feasible stimulation method during in vitro fertilization (IVF) cycle. In the beginning, in order to avoid delaying cancer treatment, LPOS was applied for fertility preservation of cancer patients, showing no difference in numbers of oocyte retrieved, mature oocytes and fertilization rate between luteal or follicular phase stimulation. In the recent, LPOS was used for infertility women, suggesting that LPOS owned quite good IVF outcomes. In previous studies, premature luteinizing hormone (LH) surge, a major reason worsening ovarian quality in poor ovarian responders (PORs), was seldom found in LPOS. High progesterone in luteal phase may aid in suppressing premature LH surge. An updated research claimed that numbers of oocyte retrieved, mature oocytes and fertilized oocytes in LPOS significantly increased when compared to follicular ovarian stimulation. Therefore, the investigators presumed that LPOS was a more effective method than follicular stimulation in PORs.

Official Title
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Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital

Conditions
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Fertilization in Vitro

Intervention / Treatment
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* Other: luteal ovarian stimulation
* Other: follicular ovarian stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Poor ovarian responders (PORs) met the Bologna criteria, having at least two of the three following features: advanced maternal age (≥ 40 years) or any other risk factor for POR, a previous POR (≤ 3 oocytes with a conventional stimulation protocol), and an abnormal ovarian reserve test. An abnormal ovarian reserve test was defined as antral follicle count (AFC) < 5 or anti-Müllerian hormone (AMH) < 1 ng/mL in this study. Moreover, two episodes of a previous POR after maximal stimulation alone would be sufficient to define a patient as a POR. Exclusion Criteria: oophorectomy exposure to cytotoxic or pelvic irradiation for malignancy taking herbal drugs or other hormonal agents

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: luteal ovarian stimulation<br>The controlled ovarian stimulation in in vitro fertilization cycle was started since luteal phase. | Other: luteal ovarian stimulation<br>* In the in vitro fertilization cycle, controlled ovarian stimulation was started since the luteal phase.<br>|
| Active Comparator: follicular ovarian stimulation<br>The controlled ovarian stimulation in in vitro fertilization cycle was started since early follicular phase phase. | Other: follicular ovarian stimulation<br>* In the in vitro fertilization cycle, controlled ovarian stimulation was started since the follicular phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| oocytes and embryos | retrieved oocytes in number, matured oocytes in number, fertilized oocytes in number, day 3 embryos in number, top-quality day 3 embryos in number | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pregnancy rate | Clinical pregnancy rate | Pregnancy will be confirmed 4 weeks after embryo transfer. | 
| genes expression | cumulus cells genes expression | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antagonist protocol, In vitro fertilization, Poor ovarian responder, Luteal ovarian stimulation, Cumulus cells