Clinical trial NCT05402605: AOA Versus Non-AOA in Low Prognosis Patients by the POSEIDON Criteria
Official title: The Effectiveness and Safety of Artificial Oocyte Activation With Calcium Ionophore in Low Prognosis Women Classified as POSEIDON Group 4: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: in Vitro Fertilization
Keywords: POSEIDON
in vitro fertilization
live birth
low prognosis
AOA
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
First posted: 2022-06-02
Enrollment: 528
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Poor ovarian response (POR) remains one of the significant challenges of Assisted Reproductive Technology (ART). Facing difficulties related to clinical practice, optimizing the embryo culture process is necessary to improve the embryo number and quality in this group of patients. Potential techniques mentioned in the current literature include follicular size at trigger, dual trigger, artificial oocyte activation (AOA), blastocyst transfer, and the role of preimplantation genetic testing for aneuploidy (PGT-A). AOA is currently expected to improve treatment outcomes in poor ovarian responders with the potential for clinical efficacy. However, this issue has not been evaluated before.

Detailed description: Poor ovarian response (POR) remains one of the significant challenges of Assisted Reproductive Technology (ART). Patients with POR yield a low number of oocytes, leading to a low number of useable embryos and a decline in the live birth rate. According to the consensus of the European Society of Human Reproduction and Embryology (ESHRE) in 2011, POR was diagnosed using Bologna criteria. However, some recent studies show the classification by Bologna is not efficient, because the oocyte number should be combined with female age since the likelihood of achieving a live birth among patients with similar oocyte yield ultimately depends on the age of the patient. In 2016, POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) Group was established and released the new criteria. The POSEIDON criteria proposed a shift from the terminology of POR to the concept of low prognosis. According to POSEIDON criteria, low prognosis account for 30-40% of all stimulated in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. The low prognosis patient is classified into four groups according to the results of ovarian reserve markers (AMH, AFC, or both), female age, and the number of oocytes retrieved in previous cycles, such as: maternal age \< 35, AMH ≥ 1,2 ng/ml and AFC ≥ 5 (subgroup 1a: \< 4 oocytes; subgroup 1b: 4-9 oocytes); maternal age ≥ 35, AMH ≥ 1,2 ng/ml and AFC ≥ 5 (subgroup 2a: \< 4 oocytes; subgroup 2b: 4-9 oocytes); maternal age \< 35, AMH \< 1,2 ng/ml and AFC \< 5; maternal age ≥ 35, AMH \< 1,2 ng/mL and AFC \< 5. Although many efforts have been made to improve treatment outcomes in this group of patients, such as researching, understanding, and modifying clinical ovarian stimulation regimens, the results are still not feasible. Especially, group 4, which have advanced maternal age (≥ 35) and seized for 14.4% of low prognosis, has a low cumulative live birth rate (11% in group 4). Female age is a critical element in the POSEIDON classification because age is crucially related to embryo ploidy and more importantly live birth outcome. The probability of having embryo ploidy sharply declined after the age of 34 and was lower than 50% in women aged 35 years and over. Therefore, patients in group 4 will have an increased risk of aneuploidy embryos, decreasing the live birth rate in these groups of patients. A recent study evaluated cumulative live birth rates per cycle, there was a remarkable difference between POSEIDON patients (21, 43, 10, 25, 29, and 17% in groups 1a, 1b, 2a, 2b, 3, and 4, respectively) and non-POSEIDON counterparts (52%). Facing difficulties related to clinical practice, optimizing the embryo culture process is necessary to improve the embryo number and quality in the POR group. Potential techniques include follicular size at the trigger, dual trigger, artificial oocyte activation (AOA), blastocyst transfer, and the role of preimplantation genetic testing for aneuploidy (PGT-A).

In Vietnam, AOA was first reported in 2011, performing on 1588 oocytes, and said the fertilization rate was higher in the ICSI - AOA than in the ICSI group (80.8% vs 74.3%, respectively; p\<0.002).

AOA is expected to improve treatment outcomes for low prognosis patients, especially in group 4 by the POSEIDON criteria with the potential for clinical efficacy and safety. Therefore, this study aims to evaluate the effectiveness and safety of AOA on treatment outcomes in low prognosis patients defined by the POSEIDON criteria (2016).

Eligibility criteria: Inclusion Criteria:

* Was diagnosed as low prognosis patients by the POSEIDON criteria in group 4: maternal age ≥ 35 years old, AMH \< 1,2 ng/ml and AFC \< 5
* Cycles ≤ 3
* Oocytes could be collected with OPU procedure
* Ovarian stimulation with GnRH antagonist protocol
* Agree to participate in the randomization

Exclusion Criteria:

* Uterine abnormalities such as unicornuate, bicornuate uterus, didelphys and adenomyosis
* Recent history of any current untreated endocrine abnormality
* Gonadotropin resistance syndrome
* Contraindications of gonadotropins
* Absolute asthernozoospermia
* Cryptozoospermia
* Surgical sperm retrieval
* Previous low fertilization (\< 30%)
* Globozoospermia
* Cycles using donor oocytes
* Preimplantation Genetic Testing (PGT) cycles

Primary outcomes:
measure: Live birth rate
timeFrame: At 24 weeks of gestation
Secondary outcomes:
measure: Fertilization rate
timeFrame: One day after oocyte retrieval
measure: Fertilization failure rate
timeFrame: One day after oocyte retrieval
measure: Abnormal fertilization rate
timeFrame: One day after oocyte retrieval
measure: Total embryos on day 3
timeFrame: Three days after oocyte retrieval
measure: Good quality day 3 embryo rate
timeFrame: Three days after oocyte retrieval
measure: Total embryos blastocyst
timeFrame: Five days after oocyte retrieval
measure: Good quality blastocyst rate
timeFrame: Five days after oocyte retrieval
measure: Positive pregnancy test
timeFrame: At 2 weeks after embryo placement
measure: Implantation rate
timeFrame: At 3 weeks after embryo placement
measure: Cumulative implantation rate at 12 months
timeFrame: 12 months after randomization
measure: Clinical pregnancy
timeFrame: At 7 weeks after embryo placement]
measure: Cumulative clinical pregnancy at 12 months
timeFrame: 12 months after randomization
measure: Ongoing pregnancy
timeFrame: At 12 weeks after embryo placement
measure: Cumulative ongoing pregnancy at 12 months
timeFrame: 12 months after randomization
measure: Ectopic pregnancy
timeFrame: At 12 weeks of gestation
measure: Cumulative ectopic pregnancy at 12 months
timeFrame: 12 months after randomization
measure: Miscarriage
timeFrame: At 12 weeks of gestation
measure: Cumulative miscarriage
timeFrame: 12 months after randomization
measure: Multiple pregnancy
timeFrame: At 6 to 8 weeks' gestation
measure: Cumulative multiple pregnancy
timeFrame: 12 months after randomization
measure: Vanishing twins
timeFrame: At 12 weeks' gestation
measure: Cumulative vanishing twins
timeFrame: 12 months after randomization
measure: Multiple delivery
timeFrame: At 24 weeks' gestation
measure: Cumulative multiple delivery
timeFrame: 12 months after randomization
measure: Hypertensive disorders of pregnancy
timeFrame: At 20 weeks of gestation or beyond after the completion of the first transfer
measure: Gestational diabetes mellitus
timeFrame: At 24 to 28 weeks of gestation
measure: Cumulative live birth rate
timeFrame: At 24 weeks of gestation
measure: Birth weight
timeFrame: At the time of delivery
measure: Low birth weight
timeFrame: At birth
measure: Major congenital abnormalities
timeFrame: At birth
measure: High birth weight
timeFrame: At birth
measure: Very low birth weight
timeFrame: At birth
measure: Large for gestational age
timeFrame: At birth
measure: small for gestational age
timeFrame: At birth
measure: Very high birth weight
timeFrame: At birth
measure: Antepartum haemorrhage
timeFrame: At birth
measure: Perinatal mortality
timeFrame: 24 weeks of gestation to the end of the neonatal period of 4 weeks after birth
measure: Admission to NICU
timeFrame: At birth
Other outcomes:
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: IVFMD, My Duc Hospital
Study officials:
affiliation: Mỹ Đức Hospital
name: Tuong M Ho, M.D
role: PRINCIPAL_INVESTIGATOR
References: