"Hello, Dr. Wang. Remember me? I'm Xiaoman, I'm 18 weeks pregnant, and I'm here to get an amniocentesis!"
Early in the morning, a voice of joy came from the genetic clinic of the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University (Henan Provincial Maternal and Child Health Hospital). Looking at Xiao Man (pseudonym), whose face was full of happiness and happiness in front of him, Dr. Wang Jingyan's thoughts instantly returned to a year ago......
01
Xiaoman's worries
In May 2023, Xiaoman and her husband, who were trying to conceive, walked into the genetic clinic for the first time, and they were full of panic and anxiety, because she found out that she carried the F8 gene intron 22 inversion, which can cause hemophilia, and Xiaoman's uncle and father both died early due to hemophilia. In fact, she also consulted other doctors in the outer hospital and knew that she was only a carrier and generally did not get sick. But she was still afraid that her child would inherit hemophilia. Hearing that the three generations of test tubes can block the transmission of genetic diseases and avoid the birth of diseased children, she and her husband mustered up the courage to come to the consultation.
In fact, Xiaoman's concern is not unreasonable, according to the law of heredity, 50% of her offspring are hemophiliacs, and 50% of girls are carriers.
02
Knowledge of hemophilia
As shown in the figure above, hemophilia is a group of X-linked recessive hereditary bleeding disorders, theoretically, 50% of females are carriers and 50% are normal, and 50% of males are hemophiliacs, and 50% are normal. The offspring of male hemophilia patients are all carriers in females and normal in males.
Male patients generally have typical clinical manifestations, and female carriers usually have no clinical manifestations, but due to the possibility of normal X chromosome inactivation in female carriers, very few female carriers will have relevant clinical manifestations in the case of extreme bias of X chromosome inactivation.
The clinical manifestations of hemophilia are spontaneous bleeding from joints, muscles, internal organs, and deep tissues or after minor trauma, and often begins in childhood. Current treatments can effectively reduce the rate of disability and improve the quality of life, but they cannot completely cure it.
03
Start the road of three generations of test tubes
How to have a child who does not have hemophilia?
This became a question that the couple desperately wanted to know. Professor Yang Rujing, who received the consultation, carefully interpreted the genetic test results, asked about the family history in detail, and conducted a remote consultation with the genetic experts, and agreed that reproductive intervention can be carried out through the third generation of test-tube PGT-M.
PGT-M, that is, preimplantation genetic testing of single-gene disease embryos, is mainly suitable for single-gene disease patients/carrier couples, to test the target gene of embryos, and select embryos that do not carry disease-causing genes or carry disease-causing genes but do not develop the disease for transfer, so as to avoid the birth of children.
After consultation, Xiaoman and his wife considered doing three generations of IVF to avoid the "curse" of hemophilia.
However, new worries have arisen: "Will we carry other disease-causing genes? What if my child doesn't have hemophilia and then has other serious monogenic diseases?"
The genetic clinic also provided the couple with a test item for eugenics and fertility - the combined testing of whole exons for couples (screening for carriers of monogenic genetic diseases), which can screen more than 20,000 genes. If a clear causative gene is identified, genetic counseling can be carried out in a timely manner to determine whether it can be blocked. Fortunately, the couple did not find out other pathogenic genes, and they were finally able to relax and prepare for the third generation of test tubes.
After a detailed understanding of the process, costs and associated risks of PGT-M surrogacy, the road of three generations of surrogacy for the Xiaoman couple officially began. Comprehensive physical examination, stimulation medication, egg retrieval, sperm retrieval, blastocyst biopsy, embryo freezing, single-cell gene amplification, gene sequencing...
04
PGT-M Fertility Process
After years of waiting, the good news finally came: none of the 2 euploid embryos carried the maternal mutation of the F8 gene! This means that Xiaoman no longer has to worry about her child suffering from hemophilia due to the problem of the F8 gene!
What's even happier is that the embryo thawed and transferred, a successful pregnancy, and now it is 18 weeks pregnant, Xiaoman said happily, and after the baby is born, he must come to report the good news!
05
World Hemophilia Day
April 17, 2024 is the 36th "World Hemophilia Day", with the theme of "Understanding Bleeding Disorders, Actively Preventing and Treating Bleeding Diseases", aiming to raise the awareness and attention of the whole society to hemophilia and other bleeding diseases, and promote scientific prevention and standardized diagnosis and treatment.
The Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University has opened a professional genetic counseling clinic, where 86 kinds of monogenic diseases have been blocked by PGT-M technology, and the clinical pregnancy rate can be as high as 88.9%, and the babies with monogenic diseases successfully blocked by PGT technology have been born one after another. Patients who need it can come for consultation. I hope that every hemophilia family will be like Xiaoman, scientific fertility, less detours, and usher in the dawn of a new life as soon as possible!
(Some pictures come from the Internet, if there is any infringement, please contact to delete.) Submission Email [email protected])
Photo: Tian Xinxian, Reproductive Health Hospital
Reviewer: Wang Jingyan
Editor: Ji Bingbing
Editor-in-charge: Zhang Limin
Review: Hua Xiaoya