IVF INFERTILITY that occurs in both men and women

ART

1. IN VITRO FERTILIZATION GEORGE ITORO OKU

2. History of In vitro Fertilization It began with many theories, and continued with research on in vivo and in vitro fertilization in a number of different animal species. Finally in the 1960s the research progressed to human IVF, which culminated in the birth of Louise Brown on 25 July 1978 in England - the World’s first “Test-Tube Baby”. The first successful birth of a "test tube baby" named, Louise Brown, was born in 25 July, 1978 in London as a result of natural cycle In-vitro fertilization (IVF). Robert G. Edwards, the physiologist who developed the treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. He had worked earlier with Patrick Steptoe

3. The real advances in human IVF were made due to the much simpler technique of laparoscopy. This enabled the gynaecologists to see ovaries and developing follicles clearly and later to aspirate oocytes from the follicles. It was this need for gynaecologists and embryologists to work as a team that brought Patrick Steptoe and Robert Edwards together – a collaboration that, after ten years of research, culminated in the delivery of Louise Brown in July 1978, the first child to be born as a result of in vitro fertilization.

4. Aristotle, some 300 years BC, believed that it took “seed” from both a man and a woman to create children; Aristotle (384-322 BC) proposed the theory that children are a product of “the mingling of male and female seed”. This opposed the prevailing theory that children were from the male seed and women were merely the “receptacle for the child”.

5. William Harvey (1578-1657) studied the fertility of the King’s herd of deer, and wrote: “De generatione animalium ” in 1651, in which occurs the well-known phrase: “Ex ovo omnia ” – “from the egg is everything”. Antonio van Leeuwenhoek (1632-1723) carried out the first studies on human sperm with the newly invented microscope.

6. When the key discoveries were made of the existence and importance of the female’s egg and the function of sperm in the seventeenth century, the science of human reproduction really advanced. This was also, for obvious reasons, closely associated with the discovery of the microscope

7. IN VITRO FERTILIZATION (IVF) Is a method of assisted reproduction in which a man’s sperm and a woman’s eggs are combined outside of the body in a laboratory dish. One or more fertilized eggs ( embryos ) may be transferred into the woman’s uterus, where they may implant in the uterine lining and develop.

8. The basic steps in an IVF treatment cycle are Ovarian stimulation Egg retrieval Fertilization Embryo culture Embryo transfer

9. Ovarian Stimulation During ovarian stimulation, also known as ovulation induction, medications or “fertility drugs,” are used to stimulate multiple eggs to grow in the ovaries rather than the single egg that normally develops each month.

10. Medications for Ovarian Stimulation • human menopausal gonadotropin ( hMG ) • follicle-stimulating hormone (FSH) • luteinizing hormone (LH) (used in conjunction with FSH) • human chorionic gonadotropin ( hCG ) • clomiphene citrate • letrozole   Medications to Prevent Premature Ovulation • Gonadatropin -releasing hormone ( GnRH ) agonists • GnRH antagonists Clomiphene citrate and letrozole are administered orally while the other medications listed are given by injection.

11. Egg Retrieval Egg retrieval is usually accomplished by transvaginal ultrasound aspiration, a minor surgical procedure that involves insertion of ultrasound probe into the vagina to identify the follicles, and a needle is guided through the vagina and into the follicles. The eggs are aspirated (removed) from the follicles through the needle connected to a suction device. Removal of multiple eggs can usually be completed in less than 30 minutes.

12. Laparoscopy may then be used to retrieve the eggs using a small telescope placed in the umbilicus. A surgical procedure that allows viewing of the internal pelvic organs. During the procedure, a long, narrow, fiber optic instrument, called a laparoscope, is usually inserted through an incision in or below the woman'snavel .

13. Embryo Transfer One or more embryos suspended in a drop of culture medium are drawn into a transfer catheter (a long, thin sterile tube) with a syringe on one end. The physician gently guides the tip of the transfer catheter through the cervix and places the fluid containing the embryos into the uterine cavity. The maximum number of embryos transferred is based on the patient’s age and other individual patient and embryo characteristics

14. Fertilization and Embryo Culture After the eggs are retrieved, they are examined in the laboratory for maturity and quality. Mature eggs are placed in an IVF culture medium and transferred to an incubator to await fertilization by the sperm.Fertilization may be accomplished in two ways: By insemination, where motile sperm are placed together with the oocytes and incubated overnight or By intracytoplasmic sperm injection (ICSI), where a single sperm is directly injected into each mature egg

15. Visualization of two pronuclei the following day confirms fertilization of the egg. One pronucleus is derived from the egg and one from the sperm ( Motoko and Tetsuya, 2014). By the third day, a normally developing embryo will contain approximately 6 to 10 cells. By the fifth day, a fluid cavity forms in the embryo, and the placenta and fetal tissues begin to separate. An embryo at this stage is called a blastocyst . Embryos may be transferred to the uterus at any time between one and six days after the egg retrieval. If successful development continues in the uterus, the embryo hatches from the surrounding zona pellucida and implants into the lining of the uterus approximately 6 to 10 days after the egg retrieval.

16. VARIATIONS OF IVF Gamete intrafallopian transfer (GIFT) : is similar to IVF, but the gametes (egg and sperm) are transferred to the woman’s fallopian tubes rather than her uterus, and fertilization takes place in the tubes rather than in the laboratory. Another difference is that laparoscopy, a surgical procedure, is necessary to transfer the sperm and egg to the tubes. GIFT is an option only for women who have normal fallopian tubes. Some couples may consider GIFT for religious reasons because eggs are not fertilized outside the body. One limitation of GIFT is that fertilization cannot be confirmed as with IVF.

17. Zygote intrafallopian transfer (ZIFT): This technique differs from GIFT in that fertilization takes place in the lab rather than the fallopian tube, but is similar in that the fertilized egg is transferred to the tube rather than the uterus. This procedure also requires a laparoscopy.

18. Embryo Freezing (Cryopreservation) and Storage: Embryo freezing and storage (cryopreservation) consists of placing embryos at a very low temperature and storing them for prolonged periods in liquid nitrogen. During freezing, chemical solutions ( cryoprotectants ) replace water, protecting embryos from damage by ice formation. When embryos are thawed, water replaces cryoprotectants . Why are embryos frozen? To avoid an excessively high risk of multiple pregnancies, only 1 or 2 embryos are placed into the uterus during an In vitro fertilization (IVF) cycle Embryos must meet certain criteria with respect to quality to be frozen. Not every couple will have excess embryos to freeze. At what stage are embryos frozen? Embryos can be frozen at either the 6-8 cell stage (day 3) or blastocyst stage (day 5 or 6). In our clinic, most embryos are frozen as blastocysts .

19. Complications of In-Vitro Fertilization (IVF) Procedure The major complication of IVF is the risk of multiple births which is directly related to the practice transferring of multiple embryos A risk of ovarian stimulation observed as ovarian hyperstimulation syndrome (OHSS), particularly if human chorionic gonadotropin ( hCG ) is used for inducing final oocyte maturation which results in occurrence of swollen, painful ovaries in 30% of patients ( Lutgens et al ., 2009).

20. During ovum retrieval, there is small chance of bleeding, infection, and damage during transvaginal ultrasound aspiration especially in bowel and bladder as well as difficulty in breathing, chest infection, allergic reactions to meds, or nerve damage was observed in some cases too during laparoscopy. Ectopic pregnancy may also occur if fertilized ova develop outside the uterus, usually in the fallopian tubes which increases the chance of immediate destruction of the foetus . Sometimes, negative pregnancy test after IVF is associated with an increased risk for depression in women which may be leads to be increased risk of developing anxiety disorders in some cases too but it happens rarely.

21. Success Rates in In-Vitro Fertilization (IVF) The most current data available in the United States a 2009 summary was compiled by the “American Society for Reproductive Medicine” which reported the average national IVF success rates per age group using non-donor ova (Clinic Summary Report, 2009)

22. INFERTILITY

23. For women, these include: • Coordination between the hypothalamus, pituitary, and ovary to allow development of (usually) a single dominant egg ( oocyte ); • Preparation of the lining of the uterus (the endometrium ) to receive an embryo; • Release of the egg (ovulation) from the ovary; • “Capture” of the egg by the fallopian tube; • Interaction with sperm within the tube resulting in fertilization; • Transport of the fertilized egg (zygote) through the tube and into the uterine cavity, as the zygote divides and becomes a multi-cell embryo; and • Implantation of the embryo into the endometrium , and development of the placenta.  

24. For men, the steps include: • Production of sperm in sufficient number and of sufficient motility to allow enough travel from the vagina through the cervix and uterus into the fallopian tube; and • Fertilization itself, which involves a complex chemical interaction between sperm and egg. Conditions that affect any of these processes reduce the chances of conception in a given cycle; if the condition is chronic, it can lead to the clinical condition of infertility.

25. Normal reproduction

26. INFERTILITY The most commonly used definition of infertility is at least 12 months of unprotected intercourse without conception used in everything from population-based surveys to clinical practice recommendations (Chandra et al ., 2005). Assisted reproductive technology (ART) involves all treatments or procedures that include the in vitro handling of human oocytes and sperm or embryos for the purpose of establishing a pregnancy. Infertility is exclusively due to a female factor in 35 to 40% of couples. Approximately 21% to 45% of female infertility (15% of all infertility in couples) is due to ovulatory disorders. Ovulatory disorders may be caused by various factors, including aging or premature ovarian failure, endocrine dysfunction, stress, excessive exercise or weight loss, or tobacco use.

27. Among men, most cases of infertility are a consequence of abnormal or too few sperm. It is regarded as psychologically stressful by most individuals and can lead to depression, social isolation and a lower quality of life ( Johansson et al ., 2009). The public health burden of these births is compounded by the fact that the advancing technology of ART, combined with the use of eggs donated by young women, increasingly allows women beyond the traditional reproductive ages (15–44 years) to achieve pregnancy and livebirth ( Kinzler et al ., 2000). Infertility indicates a difficulty in conceiving or carrying a pregnancy to term.