ICSI Versus Conventional IVF in Couples With Non-severe Male Infertility

Study Overview
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Brief Summary
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A multicenter, parallel-controlled(1:1 treatment ratio), open-label, randomized clinical trials regarding fertilization and pregnancy outcomes between ICSI and conventional IVF among couples with no-severe male-factor infertility in China.

Detailed Description
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A multicenter, large-scale, randomized controlled clinical trial will enroll 2,346 couples with non-severe male infertility undergoing their first or second cycle of IVF or ICSI. The study will recruit participants from 6 Reproductive Medical Centers across mainland China.The participation in this study will be approximately 2 years with a total of 7 visits from controlled ovarian hyperstimulation, pregnancy to delivery. On the day of oocyte retrieval, eligible participants will be allocated to two groups at a ratio of 1:1- ICSI protocol, and conventional IVF protocol. All participants will be randomized through stratified block randomization according to the study sites.

Official Title
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Intracytoplasmic Sperm Injection (ICSI) Versus Conventional in Vitro Fertilization (IVF) in Couples With Non-severe Male Infertility: a Randomized Controlled Trial

Conditions
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Male Infertility

Intervention / Treatment
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* Other: ICSI
* Other: Conventional IVF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infertile couples scheduled for their first or second IVF/ICSI cycle. Men with non-severe male infertility: Sperm concentration 5,000,000-15,000,000/ml or sperm with progressive motility (type A+B) 10-32%. Women received either gonadotrophin-releasing hormone agonist protocol or gonadotrophin-releasing hormone antagonist protocol as their controlled ovarian hyperstimulation treatment. Informed consent obtained. Exclusion Criteria: Couple with contraindication for IVF or ICSI. Couples receiving donor sperm or donor eggs. Couples undergoing PGD and PGS. Sperm concentration with progressive motility used for insemination <100,000/ml on the day of oocyte retrieval. Women with 0 oocytes after oocyte retrieval. Using frozen semen. Poor fertilization in previous cycle (≤ 25%).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible patients that have provided informed consent will be randomized to either ICSI or conventional IVF. Randomization and allocation of patients to study groups will be performed on the day of oocyte retrieval. Stratified permuted block randomization will be centrally controlled by administrative staffs in the trial center, who are not involved in the treatment procedure. When there is an eligible participant to be enrolled into the study, nurses from the specific site will login the trial system to get allocation of patients according to a computer-generated randomization list in a 1:1 ratio, with a variable block size of 2, 4 or 8 and stratified by center.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intracytoplasmic Sperm Injection<br>On the day of oocyte retrieval, qualified participants will be randomized into either of two groups. Participants in group A will undergone Intracytoplasmic Sperm Injection (ICSI) procedure, other standard assisted reproductive treatments are similar and parallel between two groups. | Other: ICSI<br>* All patients will receive controlled ovarian hyperstimulation (COH) treatment, which is performed by standard routines at each study center. The COH treatment includes either gonadotrophin-releasing hormone agonist (GnRH-a) protocol or gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol.Oocyte retrieval is scheduled for 36 (±2) after hCG injection.The retrieved cumulus oocyte complexes (COC) will be allocated to undergo routine ICSI procedure according to the result of randomization in each study site.<br>|
| Active Comparator: Conventional IVF<br>On the day of oocyte retrieval, qualified participants will be randomized into either of two groups. Participants in this group will undergone Conventional In Vitro Fertilization (IVF) procedure, other standard assisted reproductive treatments are similar and parallel between two groups. | Other: Conventional IVF<br>* All patients will receive controlled ovarian hyperstimulation (COH) treatment, which is performed by standard routines at each study center. The COH treatment includes either gonadotrophin-releasing hormone agonist (GnRH-a) protocol or gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol.Oocyte retrieval is scheduled for 36 (±2) after hCG injection.The retrieved cumulus oocyte complexes (COC) will be allocated to undergo conventional IVF procedure according to the result of randomization in each study site.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy leading to live birth after the first cycle with embryo transfer | A delivery of one or more living infants (≥22 weeks gestation or birth weight more than 1,000g). | After 22 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fertilization | Number of zygotes with 2 PN (per oocyte retrieved and per women randomized). | 16-20 hours after oocyte retrieval | 
| Total fertilization failure | No oocyte formed 2 PN in this given cycle. | 72 hours after oocyte retrieval | 
| Available embryo | Number of embryos ≥4 cells and ≤30% fragmentation on day 3 observation. | 72 hours after oocyte retrieval | 
| Good quality embryo | Number of embryos with ≥6 cells and ≤30% fragmentation developed from 2PN embryos on day 3 observation. | 72 hours after oocyte retrieval | 
| Implantation | Number of gestational sacs observed per embryo transferred. | 28 days after embryo transfer | 
| Clinical pregnancy | One or more observed gestational sac or definitive clinical signs of pregnancy under ultrasonography at 7 weeks after embryo transfer (including clinically documented ectopic pregnancy). | 7 weeks after embryo transfer | 
| Multiple pregnancy | Pregnancy with two or more gestational sacs or positive heart beats at 7 weeks of gestation. | 7 weeks after embryo transfer | 
| Ongoing pregnancy | Presence of a gestational sac and fetal heartbeat after 12 weeks of gestation. | 12 weeks after embryo transfer | 
| Moderate/severe ovarian hyperstimulation syndrome (OHSS) | exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations. It is classified as mild, moderate, or severe according to the degree of abdominal distention, ovarian Enlargement, and respiratory, hemodynamic, and metabolic complications. | From date of controlled ovarian hyperstimulation until the date of oocyte retrieval, assessed about 14-16 days. | 
| Miscarriage | Spontaneous loss of an intra-uterine pregnancy prior to 22 completed weeks of gestational age. | 22 weeks of gestation | 
| Ectopic pregnancy | Implantation takes place outside the uterine cavity, confirmed by sonography or laparoscopy. | 7 weeks of gestation | 
| Gestational diabetes mellitus (GDM) |  | 24-37 weeks of pregnancy | 
| Hypertensive disorders of pregnancy | Comprising pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia. | 28-37 weeks of pregnancy | 
| Antepartum haemorrhage | Including placenta previa, placenta accreta and unexplained. | 28-37 weeks of pregnancy | 
| Preterm birth | Birth of a fetus delivered after 28 and before 37 completed weeks of gestational age in participants confirmed ongoing pregnancy. | 28-37 weeks of pregnancy | 
| Birth weight | Including low birth weight (defined as weight < 2500 gm at birth), very low birth weight (defined as < 1500 gm at birth), high birth weight (defined as >4000 gm at birth) and very high birth weight (defined as >4500 gm at birth). | Within 2 weeks after live birth | 
| Large for gestational age | Birth weight >90th centile for gestation, based on standardised ethnicity based charts. | Within 2 weeks after live birth | 
| Small for gestational age | Less than 10th centile for gestational age at delivery based on standardised ethnicity based charts. | Within 2 weeks after live birth | 
| Congenital anomaly | Any congenital anomaly will be included. | Within 2 weeks after live birth | 
| Perinatal mortality | Fetal or neonatal death occurring during late pregnancy (at 28 completed weeks of gestational age and later), during childbirth, or up to seven completed days after birth. | Within 6 weeks after live birth | 
| Neonatal mortality | death of a live born baby within 28 days of birth | Within 6 weeks after live birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Male infertility, In vitro fertilization, Intracytoplasmic sperm injection