Challenges and Management of Infertility, Including Assisted Reproductive Technologies

1. Challenges and Management of Infertility, Including Assisted Reproductive Technologies Kit S. Devine, MSN, ARNP

2. Introduction • The inability to create a desired pregnancy that culminates in the birth of a child is likely to create a life crisis for women and their partners. Women seeking fertility treatment look to nurses for care, counsel and health teaching.

3. Introduction (Continued) • Primary infertility: The inability to conceive after 1 year of unprotected intercourse for a woman younger than 35, or after 6 months of unprotected intercourse for a woman 35 or older (Speroff & Fritz, 2005). • Secondary infertility: The inability of a woman to conceive who previously was able to do so (Speroff & Fritz, 2005).

4. Introduction (Continued) • Infertility is more common in older women. However, increased age reduces the efficacy of treatment.

5. Prevalence and Overview of Treatments • The overall incidence of infertility has remained relatively unchanged for the past 30 years (Speroff & Fritz, 2005). • In 2002, about 2 percent of women of reproductive age had an infertility-related medical appointment within the previous year, and 10 percent had an infertility-related medical visit at some point in the past (Chandra et al., 2005).

6. Prevalence and Overview of Treatments (Continued) • Approximately half of all women who • receive fertility care achieve conception • leading to a live birth (Speroff & Fritz, 2005).

7. Scope of the Problem • Types of ART cycles: United States, 2004 (Speroff & Fritz, 2005)

8. Factors Influencing the Use of Fertility Services • Increased education and career opportunities for women • Increased number of providers and centers offering fertility services • Increased public awareness of infertility and treatment options

9. Causes of Infertility • Discovering which cause of infertility affects a particular couple is the basis of fertility care. • Causes are shared, almost equally, by men and women. • Mixed-factor infertility involves multiple causes, with some belonging to the man and some to the woman.

10. Causes of Infertility(Continued) • Couples (Speroff & Fritz, 2005)

11. Causes of Infertility(Continued) • Women (Speroff & Fritz, 2005)

12. Evaluation of the Woman • Primary evaluation components: • Male factor • Ovarian factor • Cervical factor • Tubal factor • Uterine factor

13. Physical Evaluation • Obtain a complete health history of both partners • Assess the woman’s hormone values • Perform a complete pelvic exam • Order the man’s semen analysis

14. Complete Pelvic Examination • Abnormalities and current pathologies are ruled out. • Discovery of abnormalities influence the management and efficacy of care. • Transvaginal ultrasound (TVUS):Used to examine the uterus, endometrium, ovaries and tubes

15. Complete Pelvic Examination (Continued) • Sonohysteroscopy: Used to identify polyps, fibroid tumors, cysts or other intrauterine masses • Hysterosalpingogram: Used to evaluate the interior uterus and fallopian tubes

16. Complete Pelvic Examination(Continued) • Endometrial cavity distended during saline hysterography Image provided by author. Reprinted with permission. (Figure 3)

17. Complete Pelvic Examination (Continued) • Tubal and peritoneal pathology are the primary problem for 30 percent to 35 percent of infertile couples (Miller et al., 1999). • Providers should know the status of the fallopian tubes before any fertility treatment begins.

18. Evaluation of Ovulatory Function • Women can use simple, noninvasive techniques to predict ovulation: • Daily basal body temperature • Ovulation predictor kits • Salivary predictor tests

19. Evaluation of Ovulatory Function (Continued) • TVUS: Evaluates ovarian follicle development and quality of the endometrial lining • Clomid Challenge Test (CCT): Assesses ovarian reserve in the older woman or the woman suspected of having early ovarian failure

20. Evaluation of Ovulatory Function(Continued) • Enlarged ovarian follicle filled with fluid and a mature ooctye Image provided by author. Reprinted with permission. (Figure 4)

21. Evaluation of Ovulatory Function (Continued) • Mature oocyte Image provided by author. Reprinted with permission. (Figure 5)

22. Evaluation of Ovulatory Function (Continued) • Anovulation and oligoovulation: • Among the most common causes of infertility • More common in women who: • Have extremes of body weight • Exercise excessively • Struggle with eating disorders

23. Ovarian Dysfunction and Failure • Some women fail to ovulate because they have very few or no remaining oocytes. • Before about age 40, this condition is classified as premature ovarian failure or premature menopause. • Using a donated oocyte or embryo adoption are the only options for affected women who desire to become pregnant.

24. Endometriosis • Strongly associated with infertility • Affects 20 percent to 40 percent of infertile women • Management methods include surgery and medication

25. Recurrent Pregnancy Loss • Chromosomal abnormalities • Uterine malformations • Immunologic factors • Thrombophilias • Endocrine abnormalities • Infectious disease • Environmental contributors

26. Factors that Affect Fertility • Chronic stress related to fertility • Smoking and exposure to secondhand smoke • Excessive alcohol intake • Illicit drug use • Extreme body mass index (BMI) • Eating disorders

27. Polycystic Ovarian Syndrome (PCOS) • Affects women with irregular menses and an inability to maintain normal BMI • Usually includes elevated levels of serum androgens, insulin resistance and chronic anovulation

28. PCOS (Continued) • Ovaries affected by PCOS Image provided by author. Reprinted with permission. (Figure 6)

29. Surgical and Radiological Evaluation • Providers should evaluate pelvic pain that is more than mild uterine cramping. • TVUS can identify or rule out reasons for pelvic pain. • Laparoscopy and hysteroscopy can evaluate and address conditions such as endometriosis, pelvic adhesions and tubal abnormalities.

30. Evaluation of the Male • Male factor contributes to infertility in 50 percent of infertile couples (Trummer et al., 2000). • Evaluation begins at the initial consultation with the couple.

31. Evaluation of the Male (Continued) • Physical examination • Obesity • Hypothalamic or pituitary failure • Abnormalities of the testes, epididymis, prostate or penis • Presence of vas deferens • Degrees of varicocele • Semen analysis • Endocrine and chromosomal assessment • Anatomical evaluation • Psychological factors

32. Fertility Treatment: Goals • To ensure patient safety • To help a couple experience a healthy pregnancy and birth or an alternative way to build a family • To use as little of a couple’s resources as necessary

33. Fertility Treatment: Options • Correct ovulatory dysfunction • Correct tubal or uterine abnormalities • Overcome subfertile sperm parameters • ART

34. Ovulation Induction: Clomiphene Citrate (Clomid, Serophene) • The “first line” of fertility therapy • Used to treat mildly disordered ovulation and luteal-phase insufficiency • Establish tubal patency and sperm adequacy before use.

35. Ovulation Induction: Clomiphene Citrate(Continued) • In appropriately selected patients, 80 percent ovulate and 40 percent conceive with clomiphene (Imani, Eijkemans, te Velde, Habbema & Fauser, 1999). • Cumulative conception rate is 60 percent to 75 percent (Dickey & Holtkamp, 1996).

36. Ovulation Induction: Clomiphene Citrate(Continued) • Multiples rate is about 10 percent (Imani, Eijkemans, te Velde, Habbema & Fauser, 2002). • After 6 months, women should move on to more aggressive therapy.

37. Ovulation Induction: Injectable Gonadotropins • Used: • When women exhibit resistance to clomiphene • When multiple oocytes are desirable to ovulate • With IVF and creation of donor oocytes and embryos • With ovulation induction (OI) • Multiple rates as high as 40 percent (Jones, 2007).

38. Ovulation Induction: Injectable Gonadotropins (Continued) • Mature ovarian follicles from gonadotropin stimulation Images provided by author. Reprinted with permission. (Figure 7)

39. Ovulation Induction: Pulsatile Gonadotropin-Releasing Hormone • Anovulation may be due to the failure of the hypothalamus to provide sufficient stimulation to the pituitary gland. • Gonadotropin-releasing hormone (GnRH) can be directly administered via a small medication pump to induce ovulation. • The ideal patient is the hypogonadotropic woman.

40. Ovulation Induction: Pulsatile GnRH (Continued) • Overall ovulation rates are between 50 percent and 80 percent. The chance of pregnancy is 10 percent to 30 percent per ovulatory cycle, depending on the couple’s other fertility factors (Gill et al., 2001). • The risk of multiples is low. The risk of moderate or severe hyperstimulation is very low (<1 percent) (Gill et al., 2001).

41. Artificial Insemination • Used to treat: • Male-factor infertility • Retrograde ejaculation • Neurologic impotence • Sexual dysfunction • Sperm used for insemination may be the male partner’s or donated.

42. Artificial Insemination (Continued) • Methods of insemination • Intracervical insemination (ICI) • Intrauterine insemination (IUI) • Success rates vary from 6 percent to 24 percent per cycle (van der Westerlaken et al., 1998).

43. Assisted Reproduction • Assisted hatching of the embryo Images provided by author. Reprinted with permission. (Figure 8)

44. Assisted Reproduction (Continued) • Indications for ART: • Tubal disease • Male-factor infertility • Endometriosis • Premature ovarian failure • Polycystic ovarian syndrome • Immunologic infertility • Unexplained infertility

45. Assisted Reproduction (Continued) • IVF: Placing the gametes and subsequent embryo into the uterus • ZIFT (zygote intrafallopian transfer): Placing the gametes and subsequent embryo into the fallopian tubes • GIFT (gamete intrafallopian transfer): Placing the unfertilized oocyte and sperm into the fallopian tube

46. Assisted Reproduction (Continued) • Stimulation type, dosage and duration depends on patient characteristics, diagnoses and the fertility center. • Monitoring is usually by serial TVUS, usually over four to five visits.

47. Assisted Reproduction (Continued) • Cleavage of the embryos and other subjective indicators of embryo health help the clinician decide timing and number of embryos to transfer. • The usual timing of transfer of embryos is on day 3, 4 or 5 after retrieval.

48. Assisted Reproduction (Continued) • Multicellular embryos Images provided by author. Reprinted with permission. (Figure 9)

49. Assisted Reproduction: Cryopreservation • Freezing, thawing and using: • Sperm • Embryos • Oocytes

50. Assisted Reproduction: Cryopreservation (Continued) • Expanded blastocysts Images provided by author. Reprinted with permission. (Figure10)