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

2. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation Introduction (Continued) Infertility is more common in older women. However, increased age reduces the efficacy of treatment.

5. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation Scope of the Problem Types of ART cycles: United States, 2004 (Speroff & Fritz, 2005)

8. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation Causes of Infertility (Continued) Couples (Speroff & Fritz, 2005)

11. © 2008, March of Dimes Foundation Causes of Infertility (Continued) Women (Speroff & Fritz, 2005)

12. © 2008, March of Dimes Foundation Evaluation of the Woman Primary evaluation components: –Male factor –Ovarian factor –Cervical factor –Tubal factor –Uterine factor

13. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation Complete Pelvic Examination (Continued) Endometrial cavity distended during saline hysterography Image provided by author. Reprinted with permission. (Figure 3)

17. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation Evaluation of Ovulatory Function Women can use simple, noninvasive techniques to predict ovulation: –Daily basal body temperature –Ovulation predictor kits –Salivary predictor tests

19. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation Enlarged ovarian follicle filled with fluid and a mature ooctye Evaluation of Ovulatory Function (Continued) Image provided by author. Reprinted with permission. (Figure 4)

21. © 2008, March of Dimes Foundation Mature oocyte Evaluation of Ovulatory Function (Continued) Image provided by author. Reprinted with permission. (Figure 5)

22. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation Endometriosis Strongly associated with infertility Affects 20 percent to 40 percent of infertile women Management methods include surgery and medication

25. © 2008, March of Dimes Foundation Recurrent Pregnancy Loss Chromosomal abnormalities Uterine malformations Immunologic factors Thrombophilias Endocrine abnormalities Infectious disease Environmental contributors

26. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation PCOS (Continued) Ovaries affected by PCOS Image provided by author. Reprinted with permission. (Figure 6)

29. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation Fertility Treatment: Options Correct ovulatory dysfunction Correct tubal or uterine abnormalities Overcome subfertile sperm parameters ART

34. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation Mature ovarian follicles from gonadotropin stimulation Ovulation Induction: Injectable Gonadotropins (Continued) Images provided by author. Reprinted with permission. (Figure 7)

39. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation Assisted Reproduction Assisted hatching of the embryo Images provided by author. Reprinted with permission. (Figure 8)

44. © 2008, March of Dimes Foundation Assisted Reproduction (Continued) Indications for ART: –Tubal disease –Male-factor infertility –Endometriosis –Premature ovarian failure –Polycystic ovarian syndrome –Immunologic infertility –Unexplained infertility

45. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation 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. © 2008, March of Dimes Foundation Assisted Reproduction (Continued) Multicellular embryos Images provided by author. Reprinted with permission. (Figure 9)

49. © 2008, March of Dimes Foundation Assisted Reproduction: Cryopreservation Freezing, thawing and using: –Sperm –Embryos –Oocytes

50. © 2008, March of Dimes Foundation Assisted Reproduction: Cryopreservation (Continued) Expanded blastocysts Images provided by author. Reprinted with permission. (Figure 10)

51. © 2008, March of Dimes Foundation Assisted Reproduction: Cryopreservation (Continued) Cryopreserved blastocysts Images provided by author. Reprinted with permission. (Figure 11)-

52. © 2008, March of Dimes Foundation Preimplantation Genetic Diagnosis (PGD) Used only with IVF One or two cells removed from the embryo and analyzed for defects before transfer to the uterus

53. © 2008, March of Dimes Foundation PGD (Continued) May be helpful for: –Women older than 35 years –Couples who have experienced recurrent pregnancy loss –Couples with one partner known to carry a balanced chromosomal translocation Up to 85 percent accurate for detecting the most common chromosomal abnormalities (Knops, 2004)

54. © 2008, March of Dimes Foundation Third-party Reproduction Donor gametes Donor embryos Surrogacy –Gestational carrier: Carries other people’s oocyte and sperm –Traditional surrogate: Inseminated with the male partner’s sperm

55. © 2008, March of Dimes Foundation Third-party Reproduction (Continued) Fertilized oocyte Image provided by author. Reprinted with permission. (Figure12)

56. © 2008, March of Dimes Foundation ART Risks and Complications Ovarian hyperstimulation syndrome (OHHS) Multiple gestation—More than 43 percent of the rise in multiple births in the U.S. is linked to ART, with 25 percent to 38 percent of treatments leading to multiple births (Jain et al., 2004).

57. © 2008, March of Dimes Foundation ART Risks and Complications (Continued) Triplet and higher-order deliveries: United States, 1996 to 2004 (NCHS, final natality data, 1996 to 2004)

58. © 2008, March of Dimes Foundation ART Risks and Complications (Continued) Twin intrauterine pregnancy 6 weeks7 weeks Images provided by author. Reprinted with permission. (Figure14)

59. © 2008, March of Dimes Foundation ART Risks and Complications (Continued) Twin intrauterine pregnancy (Continued) 9 weeks13 weeks Images provided by author. Reprinted with permission. (Figure14)

60. © 2008, March of Dimes Foundation Male-factor Infertility ART may help men with: –Sperm counts between 1 and 10 million with poor motility and morphology scores –Failed previous inseminations –Obstructive or nonobstructive azoospermia where sperm can be successfully extracted from the epididymis or testes

61. © 2008, March of Dimes Foundation Male-factor Infertility (Continued) Intracytoplasmic sperm injection (ICSI) Image provided by author. Reprinted with permission. (Figure15)

62. © 2008, March of Dimes Foundation Advanced Reproductive Age Percentage of births by maternal age: United States, 2000 to 2004 average (NCHS, final natality data, 2000 to 2004)

63. © 2008, March of Dimes Foundation Advanced Reproductive Age (Continued) Risks –Pregnancy loss at all stages of gestation –Down syndrome –Multiple births –Hypertension and gestational diabetes –Low birthweight (LBW) –Difficult labor –Cesarean birth

64. © 2008, March of Dimes Foundation Advanced Reproductive Age (Continued) Risks (Continued) –Risks associated with older childbearing are manageable. Most women can expect positive outcomes (Carolan, 2003). –Nurses should counsel women in their early 30s about fertility.

65. © 2008, March of Dimes Foundation Advanced Reproductive Age (Continued) Multiple deliveries by maternal age: United States, 2002 to 2004 average (NCHS, final natality data, 2002 to 2004)

66. © 2008, March of Dimes Foundation Adjustment to Pregnancy and Parenting Women who conceive as a result of ART: Increased risk for mood disorders during pregnancy and for early parenting difficulties (Fisher et al., 2005; Olshansky & Sereika, 2005) Women with multiple newborns: Increased risk for postpartum depression (Fisher & Stocky, 2003) Children born after ART: Increased risk of birth defects

67. © 2008, March of Dimes Foundation Financial Counseling Treatment can be expensive. Providers should ensure that clients understand all the options and costs.

68. © 2008, March of Dimes Foundation Special Role of Nursing To help reduce a woman’s anxiety, increase her knowledge and validate the significance of her experience throughout evaluation and treatment To guide the woman through grief that follows unsuccessful treatment and help her determine when it is time to stop treatment (Clapp, 2004)

69. © 2008, March of Dimes Foundation Nursing Strategies Giving anticipatory guidance Providing a quiet, private place for consultation Allowing adequate time for questions and discussion Giving patient-specific instructions Giving therapeutic touch, when appropriate

70. © 2008, March of Dimes Foundation Nursing Strategies (Continued) Maintaining personal contact during and after treatment cycles Recognizing the need for grief work Expressing positive and negative feelings Providing easy access to nursing care Follow up to discuss options and emotional status

71. © 2008, March of Dimes Foundation Summary Nurses practicing in women’s health are likely to encounter women who need accurate and compassionate information about infertility and its treatment. Knowledge of infertility diagnoses and treatment is fundamental to creating best nursing interventions for these women and their partners.