Luteal phase support after oocyte retrieval is important for F.J. because she

received a GnRH agonist in her long cycle protocol. Because the efficacy of the

parenteral and vaginal formulations is similar, the patient chooses the vaginal route

to avoid further injections. She determines that she is most comfortable with 8%

progesterone vaginal gel applied once daily and is given instructions regarding the

appropriate administration technique.

Embryo Transfer

CASE 48-2, QUESTION 9: The in vitro fertilization process using intracytoplasmic sperm injection yields

four cleavage-stage embryos. What considerations are necessary for embryo transfer?

After fertilization, timing of the embryo transfer into the uterus depends on the

stage of development. Cleavage-stage embryos are transferred 2 to 3 days

postfertilization, whereas embryos in the blastocyst stage are transferred at day 5 or

6.

51

(To reference a tool that gives a representation of the embryo at different stages,

see http://visembryo.com/baby/pregnancy1.html.) The number of embryos placed

during this process must balance the risks of a multiple gestation pregnancy with the

likelihood of successful implantation.

Multiple gestation pregnancies are associated with increased maternal and

neonatal morbidity. The mother is at risk for complications such as premature labor,

pregnancy-induced hypertension, and gestational diabetes. Preterm labor occurs in

approximately 15% of single gestation pregnancies compared with 75% of triplet

pregnancies. The neonates are more likely to experience fetal growth restriction and

require intensive care for pulmonary, gastrointestinal, and neurologic

complications.

22 Additional stressors include the financial and psychosocial

implications of raising children with complex medical needs that may persist beyond

infancy.

22

F.J. is 39 years old experiencing her first cycle of IVF. The ASRM has developed

embryo transfer recommendations to limit high-order multiple pregnancies (three or

more implanted embryos). Based upon her age, if the embryos are judged to have

good quality morphology, no more than three cleavage-stage or two blastocysts

should be transferred according to ASRM guidelines.

51 A pregnancy test will be

performed 9 to 12 days after the embryo transfer to determine the outcome of the

cycle.

Long-Term Considerations

Alternate Protocols

CASE 48-2, QUESTION 10: After careful consideration, the couple decides to transfer two cleavage-stage

embryos and reserve two for cryopreservation. Unfortunately, the embryo transfer procedure is unsuccessful

and the couple plans to pursue a second procedure. What considerations are necessary for future cycles?

p. 965

p. 966

Determining an action plan for subsequent procedures requires a thorough

evaluation of the response to therapy during the first cycle. If COS is repeated for

oocyte retrieval, hormone levels, follicular development, fertilization rates, and

numbers of viable embryos are all considered to determine whether dosage

adjustments or alternate medication protocols are necessary.

In this case, F.J. experienced adequate follicular development for oocyte retrieval

without signs of OHSS. The fertilization procedure was successful and two embryos

were cryopreserved for future procedures. The couple can choose to avoid another

stimulation process for oocyte removal and move to frozen embryo transfer.

Medications remain important for the frozen embryo transfer process, which can

occur in a natural cycle or a cycle induced through the use of estrogen and

progesterone, with or without GnRH agonists.

52

Beyond planning the actual protocol, the long-term safety of any repeated

medication exposure as well as the psychosocial effects of continuing therapy must

be considered. The time needed to gather available information and weigh all

considerations will be specific to each couple.

Psychosocial Issues

The financial impact of ART is substantial. The ASRM cites the average cost of an

IVF cycle in the United States to be between $10,000 - $15,000.

53 Costs vary widely

between clinics and many offer financial counseling and payment packages to

facilitate treatment. Additionally, the psychological stress of the diagnosis and

treatment of infertility must be considered at all stages. There is an observed

fluctuation of mood during the course of an IVF cycle, with higher stress points

identified at oocyte retrieval and pregnancy testing. This is complicated by potential

side effects of medications as well as the baseline mental health of the couple.

54 For

couples who undergo successive ART procedures, repeated failures are commonly

accompanied by feelings of grief and frustration, and psychological distress is often

the reason for discontinuing treatments. Levels of emotional distress, including

symptoms of depression and anxiety, can increase with each unsuccessful cycle. This

response appears to remit immediately with a successful pregnancy, but in those who

continue to be unsuccessful, symptoms can still be significant even 6 months posttreatment.

55

This couple should be offered individual counseling and social support that

extends beyond the initial pretreatment consultation to promote positive outcomes.

56

There are several patient-focused resources for informational fact sheets and videos

highlighting the financial, medical, and psychosocial issues of infertility (Table 48-

8).

Table 48-8

Patient-Focused Infertility Resources

Sponsor Website

Path2Parenthood http://www.path2parenthood.org/

American Society of

Reproductive Medicine

http://www.reproductivefacts.org/

Centers for Disease Control and

Prevention

http://www.cdc.gov/art/patientresources/preparing.html

Resolve: The National Infertility

Association

http://www.resolve.org/

Society for Assisted

Reproductive Technology

http://www.sart.org/

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

Key References

Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted

Reproductive Technology. 2012 Assisted Reproductive Technology: National Summary Report. Atlanta, GA: US

Department of Health and Human Services; 2014. (31)

Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for

Reproductive Endocrinology and Infertility. Optimizing natural fertility: a committee opinion. Fertil Steril.

2013;100(3):631–637. (9)

Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile

female: a committee opinion. Fertil Steril. 2015;103(6):e44–e50. (2)

Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of

ovarian reserve: a committee opinion. Fertil Steril. 2015;103(3):e9–e17. (13)

Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile

male. Fertil Steril. 2015;103(3):e18–e25. (15)

Practice Committee of the American Society for Reproductive Medicine. Use of clomiphene citrate in infertile

women. Fertil Steril. 2013;100(2):341–348. (25)

Practice Committee of the American Society for Reproductive Medicine. Gonadotropin preparations: past, present,

and future perspectives. Fertil Steril. 2008;90(Suppl 3):S13–S20. (43)

Practice Committee of the American Society for Reproductive Medicine. Ovarian hyperstimulation syndrome.

Fertil Steril. 2008;90(Suppl 3):S188–S193. (45)

Practice Committee of the American Society for Reproductive Medicine. Current clinical irrelevance of luteal

phase deficiency: a committee opinion. Fertil Steril. 2015;103(4):e27–e32. (48)

Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for

Reproductive Endocrinology and Infertility. Progesterone supplementation during the luteal phase and in early

pregnancy in the treatment of infertility: an educational bulletin. Fertil Steril. 2008;90(Suppl 3):S150–S153. (50)

World Health Organization, Department of Reproductive Health and Research. WHO Laboratory Manual for the

Examination and Processing of Human Semen. 5th ed. Geneva, Switzerland: World Health Organization Press;

2010:224. (18)

Zegers-Hochschild F et al. The International Committee for Monitoring Assisted Reproductive Technology

(ICMART) and the World Health Organization (WHO) revised glossary on ART terminology, 2009. Hum

Reprod. 2009;24(11):2683–2687. (30)

Key Websites

American Society for Reproductive Medicine. http://www.asrm.org/.

Society for Assisted Reproductive Technology. http://www.sart.org/.

COMPLETE REFERENCES CHAPTER 48 INFERTILITY

Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent

pregnancy loss. Fertil Steril. 2013;99(1):63.

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Chandra A et al. Infertility and impaired fecundity in the United States, 1982–2010: data from the National Survey

of Family Growth. National Health Statistics Reports; No 67. Hyattsville, MD: National Center for Health

Statistics; 2013.

Chandra A et al. Infertility service use in the United States: data from the National Survey of Family Growth.

National Health Statistics Reports; No 73. Hyattsville, MD: National Center for Health Statistics; 2014.

American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and the Practice

Committee of the American Society of Reproductive Medicine. Female age-related fertility decline. Fertil Steril.

2014;101(3):633–634.

Mathews TJ, Hamilton BE. Delayed childbearing: more women are having their first child later in life. NCHS Data

Brief, No 21. Hyattsville, MD: National Center for Health Statistics; 2009.

Macaluso M et al. A public health focus on infertility prevention, detection, and management. Fertil Steril.

2010;93(1):16.e1–16.e10.

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2012;98(6):1400–1406.

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fertilization (IVF) and gamete intrafallopian transfer (GIFT) outcomes. Am J Obstet Gynecol. 2006;194:369–

376.

Stanford JB et al. Timing intercourse to achieve pregnancy: current evidence. Obstet Gynecol. 2002;100(6):1333–

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