Application of Reproductive Technology in Infertility

Chinese people think very highly of carrying a son on the family name. In the Chinese society, having no child or being fertile will be a very stressful situation for a couple. At present, the infertility rate is about 15% (one in six to seven couples), i.e., there are currently half a million people suffering from infertility in Taiwan.

It is generally believed that infertility is due to the female partners; however, studies have shown that chances of female and male infertility are almost equivalent. The major female factors are obstructive fallopian tubes, ovarian ovulation disorders, endometriosis, uterine and cervical abnormalities; whereas the major male factors are abnormalspermatogenesis, poor sperm quality and quantity, etc. In addition, both genders may be infertile due to immune problems or unknown reasons. There are step-by-step instructions for the treatment of infertility. After a complete check and diagnosis of the cause of infertility, about 90% of infertile couples can successfully conceive under guided pregnancy and drug treatment. Intrauterine insemination or IVF may be considered for the rest of the patients.

Intrauterine insemination (IUI) is performed through working out the time of ovulation of the wife and delivery of selected washed sperms of the husband into the uterus. Ovulation stimulation hormones will lead to multiple ovulation in a single cycle and increase the pregnancy rate. The couples could benefit from the stimulated ovulation and precise calculation of ovulation date to reach the best result of IUI. IVF is carried out by retrieval of matured eggs from ovary after drug stimulation, at the same time, collect the sperms from the male partner, the union of sperm and egg is achieved in the laboratory under appropriate culture conditions, after that, embryos with best quality are transferred to the uterus for implantation.

The birth of the first IVF baby in Taiwan in June 1974 has caused a great shock in the society at that time.This breakthrough has shed light on infertile couples. The advancement of reproductive technology has raise the implantation rate to a new level that previously, embryo transfer was performed when the fertilized eggs develop into 4- to 8-cell stage after 2 to 3 days of in vitro culture. To optimize implantation rate, the embryos to be transfer have to develop into “blastocyst” to synchronize with theuterine environment, many embryo culture methods have be reported, for example, coculture with epidermal cells which may release growth factors to facilitate embryo development helps the embryo leaving 8-cell arrest and entering the morula or blastocyst stage. The advantage of this technique is two best embryos can be transferred, and it will end up with at most twins in which case both embryos are successfullyimplanted; largely eliminate the threat of miscarriage or premature birth. And as mentioned above, the implantation rate is enhanced by blastocyst transfer.

Excess blastocysts can also be cryopreserved using embryo freezing technology, and then thawed and implanted in the next cycle.To prevent multiple births, embryo cryopreservation is widely used in assisted reproduction technology to store excess oocytes and embryos. The viability of human embryos at 2-, 4-, and 8-cell stage is about 70%, and that of pronuclei-stage embryos are above 80%. The implantation and pregnancy rate is not affected by storage of embryos in liquid nitrogen at negative 196 ° C.

In addition to freezing embryos, sperm can also be frozen through appropriate processing. The purpose of semen freezing is to freeze the semen before medications such as the cancer treatments including radio-and chemotherapy. In addition,for patients receiving IVF, their semen have to be cryopreserved under the following conditions: the patient cannot obtain sperm on their own under psychological stress, those who have been diagnosed as abnormal semen, and those who unable to retrieve their sperm on the same day their wives undergoing egg retrieval. Sperm and egg banks are created in order to assist infertile couples in their struggle for offspring. Sperms for the donors or patients are stored in liquid nitrogen at negative 196 degrees Celsius and defreezed when necessary.The main purpose of setting up sperm banks in major reproductive medical centers is to serve the following:
 

1. infertile male diagnosed as azoospermia
2. male with genetic diseases, for example, epileptic seizure, hemophilia, chromosomal abnormality, etc
3. male with rare blood type
4. male who has planned vasectomy
5. male who is going to receive chemotherapy
6. preventive storage

In fact, sperm banks existed for 10 years in Taiwan, but there were few donors at that time. With the advance in technology, online request for healthy sperm donation are common strategies in sperm banks nowadays. However, with the increase number of infertile couples, domestic sperm banks still suffer from shortage of supplies. Not everyone can donate his sperm. Before donation, the prospective donors have to go through detailed medical examinations for no genetic or infectious disease, within the legal age, and having good quality of sperms. To proven to be HIV-negative, donated semen need to be frozen and quarantined for 180 days before release for use. Donated sperms must be used for IVF. In addition, to avoid disputes or consanguineous marriage, the information of sperm donor is strictly confidential, and the sperm donated by a person is limited to give birth to one fetus.

Compared with sperm donation, it’s more complicated to donate eggs because the donors have to undergo ovulation induction cycle before egg retrieval. The entire process of donation is complicated and time-consuming; therefore the couples who need egg donation have to pay for that. Besides the donation of entire egg, “cytoplasmic transfer” is another choice for female infertility. By “supplying nutrients”from transferring part of the cytoplasm of a healthy egg, the embryo quality and development can be improved. In terms of egg donation for those who do not have a uterus and seeking for surrogacy, based on ethical concerns, law making is currently underway. Women without a uterus will be able to have their own child once the qualification of surrogate mother qualification strictly regulated.

Moreover, for couples with genetic or chromosomal abnormalities, embryo tests were performed via chorionic villus sampling or amniocentesis after implantation previously. The entire process is about two weeks, and it ends up with an abnormal embryo, the couples will be stuck in a dilemma of giving birth to an abnormal child or abortion. Therefore, a pre-implantation diagnosis of embryos will largely prevent the struggle as well as the inheritance of genetic diseases such as sex-linked diseases, thalassemia, amaurotic idiocy, Down syndrome, into next generation. Diagnosis of these genetic diseases can be performed by skilled and sophisticated micromanipulation of 4- to 8-cell stage embryos without interfering with embryonic development. One or two blastomeres were retrieved and analyzed with molecular biological methods such as PCR and FISH, both can detect abnormal embryos in a few hours. With the combination of previously mentioned blastocyst technology, there is plenty of time for accurate genetic diagnosis, and for couples with genetic diseases, it will be feasible to implant normal embryos and give birth to healthy babies.

Despite the advances in modern reproductive technology for the treatment of infertility, most patients, irrespective of male or female, are very concerned about their infertility, some of them may be depressed or anxious. Mutual understanding and accompany will be vital to the infertile couples. At last, infertile couples should be patient with the explanation of treatment process, with the knowledge of treatment and cooperation with medical professionals, as well as reasonable expectations, the couples will be able to overcome their psychological barriers and get conceived and childbirth successfully with modern reproductive.