In Vitro Fertilization (IVF) begins with management of the follicular phase. To collect a good egg, it is essential to focus on the egg’s maturation in the ovary. This period is very long (more than 5 months), and the last 2 months are particularly important. During this period, we apply our unique method of treatment which stimulates ovulation in a setting akin to the natural one. We minimize the use of drugs to avoid disturbance in egg maturation.
From the third day of the menstrual period, follicular development is stimulated and spontaneous ovulation is suppressed using clomiphene citrate. Midway during the clomiphene treatment period, an FSH (follicle-stimulating hormone) preparation is additionally used at a low dose level to facilitate the growth of the dominant follicles. Once follicular growth is enough, a trigger is administered for oocyte maturation.
For older women and women who are low responders, another treatment method was developed in our clinic. It starts with clomiphene citrate on the third day of menstruation. It is then followed by a very low dose of human menopausal gonadotropin (HMG) to stimulate follicular development.
Carefully selected types of drugs are used at low doses to achieve body-friendly In Vitro Fertilization (IVF) while maximizing the natural principles of oocyte development.
No injection or medication is given from the 3rd day of menstruation to immediately before ovulation. Close ultrasound monitoring of follicular development and hormonal levels are utilized to time the administration of a trigger to start final oocyte maturation and ovulation. This is the simplest yet the most delicate treatment method, and it also has the least interference with the oocyte’s natural development. This adheres to nature’s process of natural selection.
Sometimes, collecting a good oocyte is difficult. This may stem from using too much ovulation inducing agents from previous treatments. The disturbed menstrual cycles are restored back to normal ones through employing our unique technique, the Kaufmann therapy, for 50 days. With this method, we attempt to collect a good oocyte for IVF.
Right before ovulation, an egg is taken out with a needle from a mature follicle. At our clinic, a fine egg needle is used to enable unanesthetized egg collection, causing less physical stress to the patient and allowing her to return home 15 minutes later. Semen is collected in the semen collection room or brought from home.
Our clinic treats male infertility as well. If sperm is not found in the semen collected, surgery is conducted to take out sperm directly from the epididymis or testis. With an operative technique based on our years of experience, the patient can return home several hours after surgery.
We began developing our unique egg collection needle in 1999. Today, we use an egg collection needle (21 or 22 gauge) half the global standard thickness (17 gauge) at our clinic. The blade at the needle tip has been processed with a special technique to minimize tissue damage.
At present, over 20,000 eggs are collected annually at the Kato Ladies’ Clinic. As a result of the improvements we have made, no accident involving bleeding has occurred during egg collection (usually, massive bleeding with blood loss over 500 ml has been reported to occur at an incidence of about 3%. In 1998, before such efforts, bleeding requiring hospitalization occurred in about one out of 500 cases. The same was experienced before at our clinic).
Our very fine needle causes minimal pain and bleeding, eliminating the need to administer general anesthesia. With this needle, egg collection can be completed in several minutes without causing physical stress. This allows the patient to return home after a short period of rest (about 15 minutes).
This is done for males whose semen does not contain sperm. A needle is used to aspirate semen from the epididymis. If no sperm is acquired from the epididymis, testicular sperm extraction (TESE) is performed. In vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) under a microscope is also possible as long as at least one sperm is available.
When an egg and sperm are available, fertilization is performed. Usually, a sufficient amount of processed sperm is placed together with the egg in a dish. In case fertilization is unlikely to occur with this method, ICSI is performed under a microscope. The fertilized egg is returned into the uterus usually after 2 days of culture in vitro. Depending on the case, culture is performed for a longer period until the blastocyst has formed.
This method is done for cases where the fertilization rate is unacceptably low because of problems in the number or shape of the sperm. A sperm is directly injected into the egg to induce fertilization. Presently, we use an ICSI technique enabling a gentler and smoother injection of sperm into the egg.
The fertilized egg is cultured for 5 or 6 days, longer than usual, until the egg grows to the blastocyst. Although the egg sometimes fails to grow to the blastocyst, the implantation rate with the blastocyst is twice as high than with the ordinary 4-cell stage embryo. This method is very effective in cases where the woman has oviduct abnormalities or has undergone unsuccessful embryo transfers several times before.
This pertains to the removal of the clear zone (zona pelucida) around the blastocyst at the time of its transfer. This can improve the implantation success rate in cases where oviduct-associated abnormalities are anticipated (such as cases with a history of extrauterine pregnancy), cases where embryonic growth is slow, and cases where embryo transfer is done under hormonal adjustment.
The fertilized egg cultured in vitro is returned into the uterus. Usually, a small tube called a catheter is used to transfer the fertilized egg under ultrasonic guidance. If the endometrium cannot readily accept the fertilized egg, the egg is cryopreserved and transferred into the endometrium at a later and more appropriate point of time.
A fine soft catheter (size 2 French) made of silicone is used to transfer the embryo into the endometrial cavity.
Kato Ladies Clinic (KLC) has been attempting to reduce multiple pregnancies for many years now. At present, only one embryo (fertilized egg) is returned into the uterus at a time in all cases. In Kato Repro Biotech Center (KRBC), we will adopt the KLC way.
Abnormalities in the endometrium can hinder implantation of the embryo into the wall of the uterus. If any endometrial abnormality is found, we treat it before embryo transfer using a simple and effective method. This ensures that the uterus is in optimum condition to facilitate implantation.
The cryopreserved embryo is transferred into the uterus when the uterine environment is most favorable. We make it a rule to conduct embryo transfers after taking measures to improve the endometrial condition and control hormone levels. These are done to increase the chances of pregnancy.
Eggs and embryos that aren’t used right away are cryopreserved. With the cryopreservation technique adopted at our clinic, eggs and embryos at any growth stage can be preserved with a high survival rate. The cryopreserved fertilized egg is thawed and transferred when the uterus becomes ready to accept it.
Patients with breast cancer who desire preservation of their eggs
Females who receive anti-cancer treatment are likely to undergo arrest of their ovarian function (a condition akin to menopause) due to the adverse effects of the medicine or radiation. Whether the female recovers from this menopause-like condition or enters permanent menopause is determined by multiple factors such as the type of treatment received and her age at the time of tratment. Each case is different. If menopause occurs, ovulation does not occur, and the female is unable to become pregnant with her own egg. She becomes infertile. Additionally, patients with breast cancer have treatments with some combinations of anti-cancer drugs that increase the likelihood of early menopause.
Thanks to advances in treatment methods, there has been an increase in the number of patients interested in preserving their fertility after their cancer treatments.
For preservation of fertility, studies have been conducted on two methods: direct protection of the gonads, and cryopreservation of gametes (sperm and egg) or the fertilized egg (the embryo). The technology for the latter has been advancing rapidly under the recent progressive trends in assisted reproductive therapy, and has been applied to many patients.
Under the current guidelines prepared by the Japan Society of Obstetrics and Gynecology and the Japan Society for Reproductive Medicine, cryopreservation of embryos of married couples is acceptable as a means of preservation of fertility within the framework of infertility treatment. It is also acceptable to cryopreserve the sperm of unmarried males. No formal guidelines have been published from any of these two societies concerning cryopreservation of eggs of unmarried females.
Thus, unmarried females are not covered by infertility treatment, as a rule. However, considering that the technology for egg preservation has already been established, our clinic applies cryopreservation of eggs also from unmarried females with breast cancer on the basis of the Clinic president’s policy of meeting the desires of patients about fertility preservation.