Using Preimplantation Genetic Diagnosis in Autosomal Dominant Polycystic Kidney Disease Patients: a Multicenter Clinical Trial

Study Overview
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Brief Summary
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Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic hereditary kidney disease in humans. ADPKD may affect all the generations of the ADPKD family and the probability of ADPKD is 50% in the second generation for each gender. It has been confirmed that PKD1 and PKD2 are two pathogenic genes of ADPKD. Nowadays, the investigators have established an effective gene detection technology platform for PKD1/2 gene with long fragment PCR and next generation sequencing. First, the investigators performed genetic testing in patients with clinically diagnosed ADPKD and strong fertility desire, but afraid of hereditary risk. Using Preimplantation genetic diagnosis, including multiple annealing and looping-based amplification cycles amplification technique, the investigators successfully screened out healthy embryos by In Vitro Fertilization. Then the investigators transplanted embryos returned to the parent. When the baby is born, using umbilical cord blood gene detection, the investigators confirmed that the neonates do not inherit genetic defects form parents. The investigators have succeeded in one couple. The investigators design a multicenter clinical trial to confirm those procedures efficacy and safety.

Official Title
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Efficacy and Safety of Preimplantation Genetic Diagnosis in Blocking Pathogenic Gene Inheritance for Autosomal Dominant Polycystic Kidney Disease: a Multicenter Clinical Trial

Conditions
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Polycystic Kidney, Type 1 Autosomal Dominant Disease

Intervention / Treatment
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* Procedure: Preimplantation Genetic Diagnosis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Only one ADPKD patient in one couple without gender limitation Wife has age limitation from 20 years to 35 years ADPKD ADPKD diagnosis with or without family history Find out specific pathogenic mutations in the PKD1 gene with at least one of the following: one of family patients done kidney transplantation or renal replacement therapy before 58 years old; one of family patients died of complications before 55 years old; the patient with total kidney volume more than 650ml; the patient with total kidney volume increase rate more than 6% every year; the patient's PKD1 mutation belongs to truncated gene mutation. Both husband and wife have assisted reproductive conditions and will Pregnancy compliance with Chinese laws Signed informed consent Exclusion Criteria: Active pathogenic microorganism infection, such as hepatitis B or C, HIV, pulmonary tuberculosis, giant cell virus, fungi or other contraindications for preimplantation genetic diagnosis and so on Any one of the couple has used any drugs which may lead to abnormal reproductive system function, reproductive cell abnormalities, pregnancy risk increases in the past 3 months, or has history of drug abuse Any one of the couple has malignancy The wife has uncontrolled hypertension or refractory hypertension The wife has diabetes mellitus The wife has albuminuria The wife has autoimmune disease The wife has other disorders or functional abnormalities, such as liver or renal dysfunction, which may be aggravated by pregnancy or assisted reproduction Allergy to drugs or related products which cannot avoid in our study Participating in other clinical studies in last 3 months Participants cannot follow the study program Other conditions that the researchers considered unsuitable for participation

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 35 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: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Preimplantation genetic diagnosis group<br>ADPKD patients will complete the whole process of preimplantation genetic diagnosis with healthy baby without pathogenic gene inheritance. | Procedure: Preimplantation Genetic Diagnosis<br>* Using Preimplantation genetic diagnosis, including multiple annealing and looping-based amplification cycles amplification technique, the investigators have had screened out healthy embryos by In Vitro Fertilization. Then the investigators transplanted embryos returned to the parent. Finally, participants will have healthy baby without pathogenic gene inheritance.<br>|
| No Intervention: Natural pregnancy group<br>ADPKD patients, pathogenic mutations in PKD1, have natural pregnancy without preimplantation genetic diagnosis.The investigators will perform genetic tests on the blood or umbilical cord blood of infants born between January 2014 and June 2020. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healthy baby Rate without pathogenic gene inheritance | The investigators will do umbilical cord blood gene detection for the baby to confirm with or without pathogenic gene inheritance. The investigators will compare two groups of healthy newborns rate. | through study completion, an average of 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate in pretest of preimplantation genetic diagnosis | Using couples blood to do pretest of preimplantation genetic diagnosis in Peripheral blood mononuclear lymphocyte. | through study completion, an average of 2 year | 
| Technical failure rate of preimplantation genetic diagnosis. | The rate of amniotic fluid puncture test or umbilical cord blood gene detection confirm the offspring containing pathogenic gene mutation. | Amniotic fluid puncture test (pregnancy 16 to 19 weeks ) and Birth day | 
| Oocyte retrieval rate | The proportion of good eggs obtained after ovulation induction | through study completion, an average of 2 years | 
| Good quality embryo rate | The well-developed blastocyst ratio obtained after intracytoplasmic sperm injection | through study completion, an average of 2 years | 
| Pregnancy rate | Successful pregnancy rate of transplanted embryo | Four weeks after embryo transplantation | 
| Take home baby rate | Healthy newborn birth rate in preimplantation genetic diagnosis group | Two week after neonatus birth day | 
| The total kidney volume change rate | The investigators do twice kidney MRI scan for calculating total kidney volume change rate between enroll and postpartum 6 months. | From enroll to postpartum 6 months | 
| The estimated glomerular filtration rate change | The investigators do twice serum creatinine test between enroll and postpartum 6 months, then using CKD-EPI formula to calculate eGFR. | From enroll to postpartum 6 months |