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

Not Applicable
Completed
Conditions
Polycystic Kidney, Type 1 Autosomal Dominant Disease
Interventions
Procedure: Preimplantation Genetic Diagnosis
Registration Number
NCT02948179
Lead Sponsor
Changlin Mei
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
459
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Preimplantation genetic diagnosis groupPreimplantation Genetic DiagnosisADPKD patients will complete the whole process of preimplantation genetic diagnosis with healthy baby without pathogenic gene inheritance.
Primary Outcome Measures
NameTimeMethod
Healthy baby Rate without pathogenic gene inheritancethrough study completion, an average of 2 year

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.

Secondary Outcome Measures
NameTimeMethod
Success rate in pretest of preimplantation genetic diagnosisthrough study completion, an average of 2 year

Using couples blood to do pretest of preimplantation genetic diagnosis in Peripheral blood mononuclear lymphocyte.

Good quality embryo ratethrough study completion, an average of 2 years

The well-developed blastocyst ratio obtained after intracytoplasmic sperm injection

Technical failure rate of preimplantation genetic diagnosis.Amniotic fluid puncture test (pregnancy 16 to 19 weeks ) and Birth day

The rate of amniotic fluid puncture test or umbilical cord blood gene detection confirm the offspring containing pathogenic gene mutation.

The total kidney volume change rateFrom enroll to postpartum 6 months

The investigators do twice kidney MRI scan for calculating total kidney volume change rate between enroll and postpartum 6 months.

The estimated glomerular filtration rate changeFrom enroll to postpartum 6 months

The investigators do twice serum creatinine test between enroll and postpartum 6 months, then using CKD-EPI formula to calculate eGFR.

Oocyte retrieval ratethrough study completion, an average of 2 years

The proportion of good eggs obtained after ovulation induction

Pregnancy rateFour weeks after embryo transplantation

Successful pregnancy rate of transplanted embryo

Take home baby rateTwo week after neonatus birth day

Healthy newborn birth rate in preimplantation genetic diagnosis group

Trial Locations

Locations (30)

Navy General Hospital

🇨🇳

Beijing, Beijing, China

Fuzhou General Hospital

🇨🇳

Fuzhou, Fujian, China

The First Hospital of Lanzhou University

🇨🇳

Lanzhou, Gansu, China

The First Affiliated Hospital of Anhui Medical University

🇨🇳

Hefei, Anhui, China

Peking University Third Hospital

🇨🇳

Beijing, Beijing, China

Southwest Hospital

🇨🇳

Chongqing, Chongqing, China

Sun Yat-sen Memorial Hospital of Sun Yat-sen University

🇨🇳

Guangzhou, Guangdong, China

The First Affiliated Hospital of Sun Yat-sen University

🇨🇳

Guangzhou, Guangdong, China

The Third Hospital of Hebei Medical University

🇨🇳

Shijiazhuang, Hebei, China

Hebei Province Center for Reproductive Medicine

🇨🇳

Shijiazhuang, Hebei, China

The Second Hospital of Hebei Medical University

🇨🇳

Shijiazhuang, Hebei, China

Wuhan Tongji Hospital

🇨🇳

Wuhan, Hubei, China

The First Affiliated Hospital of Zhengzhou University

🇨🇳

Zhengzhou, Henan, China

Renmin Hospital of Wuhan University

🇨🇳

Wuhan, Hubei, China

Wuhan Union Hospital

🇨🇳

Wuhan, Hubei, China

Reproductive & Genetic Hospital of CITIC-Xiangya

🇨🇳

Changsha, Hunan, China

Second Xiangya Hospital of Central South University

🇨🇳

Changsha, Hunan, China

Xiangya Hospital of Central South University

🇨🇳

Changsha, Hunan, China

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

🇨🇳

Nanjing, Jiangsu, China

The First Affiliated Hospital of Soochow University

🇨🇳

Suzhou, Jiangsu, China

The First Affiliated Hospital with Nanjing Medical University

🇨🇳

Nanjing, Jiangsu, China

Shengjing Hospital

🇨🇳

Shenyang, Liaoning, China

Hospital for Reproductive Medicine Affiliated to Shandong University

🇨🇳

Jinan, Shandong, China

Shandong Provincial Hospital

🇨🇳

Jinan, Shandong, China

Shanghai Changzheng Hospital

🇨🇳

Shanghai, Shanghai, China

Shanxi Provincial People's Hospital

🇨🇳

Chengdu, Sichuan, China

Tang-Du Hospital

🇨🇳

Xi'an, Shanxi, China

West China Hospital of Sichuan University

🇨🇳

Chengdu, Sichuan, China

West China Second University Hospital

🇨🇳

Chengdu, Sichuan, China

Sir Run Run Shaw Hospital of Zhejiang University

🇨🇳

Hangzhou, Zhejiang, China

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