Polycystic Kidney, Type 1 Autosomal Dominant Disease
Conditions
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.
Interventions
PROCEDUREPreimplantation Genetic Diagnosis
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.
Sponsors
The First Affiliated Hospital of Anhui Medical University
The First Affiliated Hospital with Nanjing Medical University
Shandong Provincial Hospital
Tang-Du Hospital
Shengjing Hospital
Second Xiangya Hospital of Central South University
Reproductive & Genetic Hospital of CITIC-Xiangya
Peking University Third Hospital
Navy General Hospital, Beijing
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
The First Affiliated Hospital of Soochow University
Sir Run Run Shaw Hospital
Fuzhou General Hospital
The First Affiliated Hospital of Zhengzhou University
Wuhan TongJi Hospital
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Renmin Hospital of Wuhan University
Xiangya Hospital of Central South University
First Affiliated Hospital, Sun Yat-Sen University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Southwest Hospital, China
LanZhou University
Shaanxi Provincial People's Hospital
West China Hospital
West China Second University Hospital
Sichuan Provincial People's Hospital
Hebei Medical University Third Hospital
Hebei Province Center for Reproductive Medicine
The Second Hospital of Hebei Medical University
Hospital for Reproductive Medicine Affiliated to Shandong University
Changlin Mei
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 35 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Healthy baby Rate without pathogenic gene inheritance | through 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
| Measure | Time frame | Description |
|---|---|---|
| Oocyte retrieval rate | through study completion, an average of 2 years | The proportion of good eggs obtained after ovulation induction |
| Pregnancy rate | Four weeks after embryo transplantation | Successful pregnancy rate of transplanted embryo |
| Take home baby rate | Two week after neonatus birth day | Healthy newborn birth rate in preimplantation genetic diagnosis group |
| The total kidney volume change rate | From 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 change | From 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. |
| Success rate in pretest of preimplantation genetic diagnosis | through study completion, an average of 2 year | Using couples blood to do pretest of preimplantation genetic diagnosis in Peripheral blood mononuclear lymphocyte. |
| 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. |
| Good quality embryo rate | through study completion, an average of 2 years | The well-developed blastocyst ratio obtained after intracytoplasmic sperm injection |
Other
| Measure | Time frame | Description |
|---|---|---|
| The incidence of infection | through study completion, an average of 2 years | the incidence of infection |
| The incidence of abortion rate | through study completion, an average of 2 years | the incidence of abortion rate |
| The incidence of ovarian hyperstimulation syndrome | through study completion, an average of 2 years | the incidence of ovarian hyperstimulation syndrome |
| The incidence of organ injuries | through study completion, an average of 2 years | the incidence of organ injuries |
Countries
China
Outcome results
None listed