Assisted Reproduction Technology

1. Assisted Reproduction Technology Presented by Abdulkareem Sultan Al-Olama

2. Introduction • Infertility is a very common condition affecting approximately 13-14% of couples in the reproductive age group. • Although this prevalence has remained stable over the last few years, the demand for infertility services has increased substantially. • This increase is due primarily to the Baby Boom generation entering into the reproductive age group at a time of highly publicized technological advances. Abdulkareem Sultan Al-Olama

3. Topics of Discussion • Definition of Infertility & ART • Common causes of infertility • Who is eligible for ART • Methodology of ovulation induction • Improving SPA • Other techniques • Counseling couple Abdulkareem Sultan Al-Olama

4. Topics of Discussion Cont’d • Failure rate • Cost effectiveness Abdulkareem Sultan Al-Olama

5. Definition of Infertility & ART • Infertility is defined classically as the inability to conceive after 1 year of unprotected intercourse. This definition is based on the cumulative probability of pregnancy: Abdulkareem Sultan Al-Olama

6. Month Monthly Probability Cumulative Probability 1 0.2 0.20 2 0.2 0.36 3 0.2 0.49 4 0.2 0.59 5 0.2 0.67 6 0.2 0.74 7 0.2 0.79 8 0.2 0.83 9 0.2 0.86 10 0.2 0.89 11 0.2 0.91 12 0.2 0.93 Definition of Infertility & ART Cont’d Abdulkareem Sultan Al-Olama

7. Definition of Infertility & ART Cont’d • ART refers to all techniques involving direct retrieval of oocytes from the ovary • ART procedures include IVF, GIFT, ZIFT, and ICSI. • The simplest ART procedure, IVF has been around for over 20 years and is perhaps the most commonly recognized ART of all procedures. Abdulkareem Sultan Al-Olama

8. Cause Couples Women Male 35% N/A Ovulatory 15% 40% Tubal 35% 40% Unexplained 10% 10% Other 5% 10% Common causes of infertility Causes of Infertility Abdulkareem Sultan Al-Olama

9. Common causes of infertility Cont’d • Female factors • Cervical factor • Ovulatory factor (PCOs) • Uterine factor (endometriosis) • Pelvic factor Abdulkareem Sultan Al-Olama

10. Common causes of infertility Cont’d • Polycystic Ovarian Syndrome (PCOS) Also known as Stein-Leventhal syndrome • Also known as hyperandrogenic chronic anovulation is a benign disorder that commonly results in infertility. • PCOS is characterized by irregular ovulation and menses, obesity, insulin resistance, acne, and hirsutism. • Most women with PCOS also have ovaries filled with multiple benign cysts. Abdulkareem Sultan Al-Olama

11. Common causes of infertility (PCOS)Cont’d • How does PCOS contribute to Infertility? • Impaired fertility is a prominent feature of PCOS. • This is believed to result from elevated insulin levels that stimulate excess androgen production by the ovaries. • The androgens cause premature follicular wasting which causes inconsistent or absent ovulation, which is associated with infertility. Abdulkareem Sultan Al-Olama

12. Common causes of infertility (PCOS)Cont’d Diagnosis: • Symptoms • Irregular or absent periods • Lack of ovulation • Weight gain • Hirsutism (excessive hair growth) • Insulin resistance • Acne • Male-pattern balding • Multiple small ovarian cysts-these may be seen by an ultrasound examination • Ancthosis nigrans (darkening of the skin at the nape of the neck and under the arms and breasts). Abdulkareem Sultan Al-Olama

13. Common causes of infertility (PCOS)Cont’d Diagnosis: • Blood Work/Hormonal Testing: • Laboratory testing is important for diagnosis but it is crucial to look at multiple values collectively. Abdulkareem Sultan Al-Olama

14. Common causes of infertility (PCOS)Cont’d Diagnosis: • Ultrasound: • Ultrasound of the pelvis is typically performed when the clinician suspects PCOS. • If >10 cysts are found in either ovary that are less than 10mm, this meets the ultrasound criteria for PCOS. Furthermore, polycystic ovaries are typically 1.5 to 3 times the normal size. • Just the presence of polycystic ovaries, without symptoms and/or consistent blood work, does not confirm a diagnosis of PCOS. Abdulkareem Sultan Al-Olama

15. Common causes of infertility (PCOS)Cont’d • Treatment • Weight Loss, Progestins, Oral Contraceptives, Anti-Androgens, GnRH agonists, Fertility drugs,Surgical therapy: • a) Ovarian wedge resection • b) Laparoscopic ovarian drilling Abdulkareem Sultan Al-Olama

16. Common causes of infertility Cont’d • Endometriosis • Endometriosis can be defined as a nonmalignant disorder in which functioning endometrial tissue is present outside the uterus. • The incidence of this disease ranges from 10-15% in women between the ages of 25 and 44 who are actively menstruating, but it also occurs in teenagers. • It is estimated that 25-50% of infertile women have this disease. Abdulkareem Sultan Al-Olama

17. Common causes of infertility (Endometriosis)Cont’d • The incidence is higher in first degree relatives of women with endometriosis, which suggests that heredity may play a role. • In addition, there is also a higher prevalence of the disease in women who delay childbearing or who are of Asian descent. Abdulkareem Sultan Al-Olama

18. Common causes of infertility (Endometriosis)Cont’d • Causes and Symptoms • The cause of endometriosis is unknown, however there are several theories. • The first theory is known as retrograde menstruation, or the movement of sloughed endometrial tissue back through the fallopian tubes and into the abdominal cavity. This tissue can then attach itself to various internal organs or tissues outside of the uterus. • Immune system dysfunction. It is believed that certain women may develop endometriosis due to deficiencies in their immune system. Abdulkareem Sultan Al-Olama

19. Common causes of infertility (Endometriosis)Cont’d • In women without endometriosis, the immune system destroys any ectopic implants that may develop. However, in women with endometriosis, there is an altered immune response and the body is unable to destroy the growth of the implants. • Furthermore, some scientists believe that endometriosis is an autoimmune disorder. This means that the body makes antibodies to endometrial cells. These antibodies may destroy the healthy endometrium found in the uterus, but are ineffective in destroying ectopic implants. Abdulkareem Sultan Al-Olama

20. Common causes of infertility (Endometriosis)Cont’d • Symptoms • Pelvic pain and cramping before and during periods • Pain during intercourse • Inability to conceive • Fatigue • Painful urination during periods • Gastrointestinal symptoms such as diarrhea, constipation, and nausea Abdulkareem Sultan Al-Olama

21. Common causes of infertility (Endometriosis)Cont’d • There are other medical conditions that have similar symptoms and should be considered prior to making a diagnosis of endometriosis. Conditions that may cause generalized pelvic pain include: • Pelvic inflammatory disease (PID) • Pelvic adhesions • Neoplasms (cancers), both benign or malignant • Ovarian torsion • Sexual or physical abuse • Other causes that are not gynecologic in nature Abdulkareem Sultan Al-Olama

22. Common causes of infertility (Endometriosis)Cont’d • How does endometriosis contribute to infertility? • The cause of infertility is believed to result from the scarring and adhesions that form in the reproductive tract as a result of inflammation. • Scar tissue and adhesions may reduce fertility by either obstructing or distorting the shape of the fallopian tubes, which in turn impedes the passage of sperm to the egg. Abdulkareem Sultan Al-Olama

23. Common causes of infertility (Endometriosis)Cont’d • In the event that sperm do reach the egg, they may encounter a hostile environment unfavorable to fertilization. • Finally, scarring from endometriosis may obstruct the fallopian tubes so that if an egg is fertilized, it may be unable to travel to the uterus for implantation. Abdulkareem Sultan Al-Olama

24. Common causes of infertility (Endometriosis)Cont’d • Diagnosis • One of two techniques may be used to confirm the diagnosis of endometriosis. Both procedures involve visualization of the pelvic cavity in order to confirm the presence or absence of ectopic implants. • laparoscopy • laparotomy • If there are any suspected ectopic implants, they are biopsied in order to determine the presence of endometrial cells. Abdulkareem Sultan Al-Olama

25. Who is eligible for ART • Women with tubal diseases • Unexplained infertility • Endometriosis • Immunologic causes for infertility • Women with premature ovarian failure • Individuals with male factor infertility (e.g., abnormalities in sperm production, function or transport or prior vasectomy) Abdulkareem Sultan Al-Olama

26. Methodology of ovulation induction Cont’d • Basically, this term refers to the use of medications to stimulate your body to produce one or more eggs. • Ovulation induction can be as simple as taking a daily pill or more complicated, like injecting fertility medications and seeing your specialist daily for necessary monitoring. The simplest form of ovulation induction involves taking clomiphene. Abdulkareem Sultan Al-Olama

27. Methodology of ovulation induction Cont’d • More potent medications, known as the gonadotropins, are available for more intensive ovulation induction. • Gonadotropins are injectable medications that are made up of a combination of follicle stimulating hormone (FSH) and luteinizing hormone (LH) or just FSH alone. • These hormones can be very helpful in getting a woman to produce and release her eggs. Abdulkareem Sultan Al-Olama

28. Methodology of ovulation induction • The success of ovulation induction in achieving a pregnancy is highly variable. It depends on the diagnosis, age, the medication being used, and numerous other factors. Abdulkareem Sultan Al-Olama

29. Improving SPA • Sperm penetration assay (SPA) is a multi-step laboratory test that offers a biological assessment of human sperm fertilizing ability. Abdulkareem Sultan Al-Olama

30. Other techniques • ZIFT • GIFT • TEST • POST • ICSI • TESE • MESA Abdulkareem Sultan Al-Olama

31. Other techniques Cont’d • ZIFT • Zygote Intrafallopian Transfer. ZIFT may be recommended if the husband has severe male fertility factor or if there has been difficulty confirming fertilization with past procedures. ZIFT has the advantages of allowing fertilization to be confirmed and it has demonstrated higher success rates than IVF when used for the appropriate indications. • One disadvantage with ZIFT is that the transfer of the zygote must be performed through a laparoscope. Abdulkareem Sultan Al-Olama

32. Other techniques Cont’d • GIFT • Gamete intrafallopian transfer was developing in 1984 as a variation of in vitro fertilization (IVF). • Gift is recommended when • unexplained infertility • infertility due to immunological factors • endometriosis • selected cases of male infertility • Tubal infertility • A requirement for the procedure is that the female partner having at least one open (patent) fallopian tube. Abdulkareem Sultan Al-Olama

33. Other techniques Cont’d • TEST • Tubal Embryo Transfer; the placing of cleaving embryos into the fallopian tube. • POST • Peritoneal Oocyte and Sperm Transfer; the placement of oocytes and sperm into the pelvic cavity Abdulkareem Sultan Al-Olama

34. Other techniques Cont’d • ICSI • Intracytoplasmic sperm injection, or ICSI, was developed to treat couples who previously had a very poor probability of achieving fertilization due to the male partner's extremely low numbers of viable sperm. • This treatment, when combined with in vitro fertilization, allows these couples a more favorable probability of achieving conception. Abdulkareem Sultan Al-Olama

35. Other techniques Cont’d • TESE • Testicular Sperm Extraction • MESA • Microsurgical Epididymal Sperm Aspiration Abdulkareem Sultan Al-Olama

36. Counseling couple • The use of skills that enable a client to recognize and identify his (sic) own problems, and the ability to help client find his own solution or resolution. • The Human Fertilization and Embryology Authority (HFEA) state in their code of practice that three sorts of counseling must be available at licensed treatment center. These are: • Support counseling • Implications counseling • Therapeutic counseling Abdulkareem Sultan Al-Olama

37. Success rates "take home baby rate" • One of the first questions that most people ask is "what is the chance for success?" The best estimate is that the birth of a live baby occurs in approximately 15-25% of women in whom embryos are transferred into the uterus. • The 1998 nationwide live birth rate as reported in the IVF-ET Registry, was 24.9%. • The corresponding rate for 1989 was 14%. Abdulkareem Sultan Al-Olama

38. Success rates Cont’d • Success varies with many factors, including the number of embryos that are transferred. • If one embryo is transferred, there is approximately a 7% chance of successful implantation; with two embryos, the success rate increases to 18%. • The rate peaks with the transfer of three to four embryos. Presently, the collection of oocytes, fertilization, and early embryo growth are accomplished with a high degree of efficiency. Abdulkareem Sultan Al-Olama

39. Success rates Cont’d • The major hurdles to success are implantation after embryo transfer and early pregnancy loss. The rate of early pregnancy loss is slightly, but not significantly, higher with ART compared to spontaneous conception. • The risk of early pregnancy loss increases with age of the female partner. Over age 40, ART success rates decline dramatically. • Pregnancy complications tend to be higher with ART pregnancies, primarily because of the much higher rate of multiple pregnancy. Abdulkareem Sultan Al-Olama

40. Success rates Cont’d • Twins occur in about 25% of ART pregnancies versus 1-2%of spontaneous pregnancies. The risk of more than a twin pregnancy is less than 5%. • To put these figures into perspective, studies have shown that the rate of pregnancy in couples with proven fertility in the past is approximately 20% per cycle. Therefore, although a figure of 15-25% may sound low, it is equal to or greater than the chance that a fertile couple will conceive in any given cycle. Abdulkareem Sultan Al-Olama

41. Cost effectiveness Abdulkareem Sultan Al-Olama

42. ? Abdulkareem Sultan Al-Olama