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INFERTILITY: Update on Evaluation & Treatment. LaTasha B. Craig, M.D. Assistant Professor Division of Reproductive Endocrinology University of Oklahoma Health Sciences Center. Objectives. Understand the different causes of infertility and the specific evaluations to diagnose each cause.

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infertility update on evaluation treatment

INFERTILITY: Update on Evaluation & Treatment

LaTasha B. Craig, M.D.

Assistant Professor

Division of Reproductive Endocrinology

University of Oklahoma Health Sciences Center

objectives
Objectives
  • Understand the different causes of infertility and the specific evaluations to diagnose each cause.
  • Comprehend the available infertility treatment options including their chance of pregnancy, complications and chance of multiple gestations.
  • Have an understanding of the process and success of in vitro fertilization (IVF) & the concerns for long term outcomes of children born from IVF.
speaker disclosure
I have no financial relationships or affiliations to disclose.

Many of the medications used in in vitro fertilization are not FDA approved for this indication.

Speaker Disclosure
considerations pre pregnancy
Considerations Pre-Pregnancy
  • Nutritional issues
  • Medical conditions
  • Medications
  • Immunization history
  • Family history and genetic risk
  • Tobacco, alcohol, caffeine & substance use
  • Occupational & environmental exposures
how to time conception
How to time conception
  • Cycle Day (CD) 1 is the first day of full-flow bleeding
  • Have intercourse every 2 -3 days (especially between CD 10-20)
  • Avoid most over-the-counter lubricants
  • Things to consider:
    • Ovulation Predictor Kits
    • Basal Body Temperature Charting
  • Things to avoid:
    • Over the counter fertility tests
    • Salivary hormone tests
    • Hormonal supplements
basal body temperature monitoring
Basal Body Temperature Monitoring
  • Newill RG, Katz M. The basal body temperature chart in artificial insemination by donor pregnancy cycles. Fertil Steril 1982 Oct;38(4):431-8
definition of infertility
Definition of Infertility
  • Failure to conceive after 1 year of unprotected intercourse
  • The exception: For women ≥ 35 years old, 6 months unprotected intercourse without conception
infertility
Infertility
  • Incidence
  • Diagnostic evaluation
  • Treatment options
historical perspective on fertility
In 1790 U.S. census, birth rate was 55 per 1000 population with avg. of 8 births per woman

1995 National Survey of Family Growth (NSGF), birth rate of 15.5 per 1000, with avg. births of 1.2 per woman

Popular explanations for declining U.S. fertility

Changing roles & aspirations for women

Postponement of marriage

Delayed age of childbearing

Increasing use of contraception

Liberalized abortion

Historical perspective on fertility

Speroff. Clinical Gynecologic Endocrinology & Infertility. Sixth edition.

hysterosalpingogram hsg
Hysterosalpingogram (HSG)

Normal

Bilateral Blocked Tubes

female infertility evaluation
Female Infertility Evaluation:

Ovulation Dysfunction

Confirm ovulation by

  • History of regular cycles
  • Symptoms of ovulation
  • Ovulation predictor kits
  • Basal body temperature
  • Progesterone level around CD 21
  • Ultrasound monitoring
ovarian aging depletion of primordial follicles
Ovarian Aging:Depletion of primordial follicles

Picture from: http://embryology.med.unsw.edu.au/Notes/images/week1/ovary/oocytenumber.jpg

slide19
Marital fertility rates by 5-year age groups

Ten various populations ranging from 17th to mid-20th century.

Menken J, Trussel J, Larsen U. Age and infertility. Science 1986;23:1389-1394.

slide20
2009 Assisted Reproductive Technology Success Rates, National Summary and Fertility Clinic Reports (CDC)
slide21
2009 Assisted Reproductive Technology Success Rates, National Summary and Fertility Clinic Reports (CDC)
assessment of ovarian reserve
Assessment of Ovarian Reserve
  • Female age
  • Cycle day 3 FSH & estradiol
  • AMH level
  • Vaginal ultrasound for antral follicles
treatment options
Treatment Options
  • Directly correcta problem if possible (i.e. thyroid tx, Bromocriptine, weight loss, etc)
  • If unable to correct the underlying problem, then use empiric treatment:
    • Intrauterine insemination (IUI or AI)
    • Ovulation Induction
    • Assisted Reproductive Technology (i.e. in vitro fertilization – IVF)
slide24
Treatment Options:

Intrauterine Insemination (IUI)

Picture from Familydoctor.co.uk

treatment options ovulation induction
Treatment Options: Ovulation Induction
  • By mouth: Clomiphene (Clomid) or Letrozole (Femara)
    • Pregnancy rate is 10% per cycle (higher in PCOS patients).
    • Risk of twins 8-10% and risk of triplets or more less than 1%
    • Side Effects: hot flushes, nausea, headaches, mood swings, blurred vision, thin uterine lining, poor cervical mucus.
treatment options ovulation induction1
Treatment Options: Ovulation Induction
  • Injectable medications: Gonadotropins (FSH, LH)
    • Pregnancy rate is 10-20% each cycle (controversial)
    • Risk of twins up to 30% and risk of triplets or more 5-10%
    • Side effects of medication are minimal because it is a natural hormone. Chance of overstimulation and canceling cycle.
adjunct to ovulation induction in pcos
1500-2000 mg/ day

May not be covered by insurance in non-diabetics

Re-introduce clomid

Adjunct to Ovulation Induction in PCOS

Metformin

  • Ovulation rates, 50-80%
  • Adhesion risk, 10-15%
  • Longest study, 5 year follow-up1 (206 patients)
    • 70% Pregnancy rate (1/2 treated)
    • 50% Live birth rate

Ovarian Drilling

1 Naether OG et al., Human Reprod 9(12):2342-9, 1994

which of the following do you believe
Which of the following do you believe:
  • All patients with PCOS should be on metformin
  • All PCOS patients wanting to conceive should be on metformin
  • Metformin is only indicated if a patient has diabetes or impaired glucose tolerance.
metformin in pcos
Metformin in PCOS

Nestler JE, et al. NEJM 338(26):1876-80, 1998

metformin in pcos1
Metformin in PCOS

Glueck CJ, et al. Metabolism Apr;48(4):511-9, 1999

is metformin more effective than clomid
Is metformin more effective than clomid?
  • Randomized controlled trial of metformin 850 mg bid vs. clomiphene citrate 150 mg qd cycle days 5-9
  • Cumulative ovulation rate not different (63 vs. 67%)
  • Pregnancy rate/cycle = 15.1% metformin; 7.2% clomiphene (p = 0.009)

Palomba et al. JCEM 90(7): 4068-74, 2005

does metformin decrease the spontaneous miscarriage rate in pcos
Does metformin decrease the spontaneous miscarriage rate in PCOS?
  • Randomized controlled trial of metformin 850 mg bid vs. clomiphene citrate 150 mg qd cycle days 5-9
  • Metformin group miscarriage = 3/31 (9.7%)
  • Clomid group miscarriage = 6/16 (37.5%)
  • P = 0.045

Palomba et al. JCEM 90(7): 4068-74, 2005

is metformin more effective than clomid1
Is metformin more effective than clomid?

Legro et al. NEJM 356,6: 551-66, 2007

what if all the tests are normal

What if all the tests are normal?

Unexplained Infertility

~10% of couples

slide37
Guzick et al. Efficacy of treatment for unexplained infertility.Fertil Steril. 1998 Aug;70(2):207-13.)

Treatment Options: Unexplained Infertility

See next slide

slide38
OU Reproductive Medicine IVF Statistics( (Delivered per embryo transfer in 2010)

% Pregnant or Delivered

Age group (years)

* A comparison of clinic success rates may not be meaningful because patient medical characteristics, treatment approaches and entrance criteria for ART may vary from clinic to clinic.

slide39
Treatment Options: In Vitro Fertilization (IVF) & ART
  • Blocked tubes
  • Severe male factor
  • Unexplained infertility
  • Endometriosis/peritoneal factor infertility
  • Failure to conceive with less aggressive treatment
  • Ovarian failure/ ovarian reserve (donor eggs)
slide40
ART Team

Office & Clinic Staff

MDs

Lab• Embryology• Andrology• Endocrine

NursingStaff

assisted reproductive technology art
Assisted Reproductive Technology—ART
  • 1978/1981 In vitro fertilization—IVF
  • 1984 Donor oocyte (egg) cycle
  • 1985 Cryopreserved Embryo Transfer
  • 1990 Preimplantation Genetic Diagnosis—PGD
  • 1992 Intracytoplasmic Sperm Injection—ICSI

As of 2004, more than 1 million children born worldwide as a result of ART

slide42
IVFLuteal Leuprolide Protocol

Transfer

Retrieval

hCG

2days

3-6days

Gonadotropins8-12 days

Lupron24-30 days

OCPs14-28 days

intracytoplasmic sperm injection icsi
Discovered “by accident” in 1991 in a Belgian IVF lab

Successfully treats almost all forms of severe male factor infertility

Intracytoplasmic sperm injection—ICSI
timing of embryo transfer
Day 3

Embryo Transfer

Day 5–6 Embryo Transfer

“Blastocyst Transfer”

Timing of Embryo Transfer

Veeck LL, Zaninovic N. An Atlas of Human Blastocysts. 1st ed. New York: Parthenon Publishing, 2003;118.

children of art possible risks
Children of ARTPossible Risks
  • Multiple pregnancy
  • Low birth weight
  • Congenital anomalies
  • Transmission of parental genetic abnormalities (e.g., male factor)
  • Imprinting defects
  • Developmental abnormalities
slide55
2009 Assisted Reproductive Technology Success Rates, National Summary and Fertility Clinic Reports (CDC)
octomom s clinic west coast ivf clinic inc

Octomom’s Clinic: West Coast IVF Clinic, Inc.

In 2007, 19 patients < 35 years old

2 became pregnant

1 delivered

Average # embryos transferred: 4.1

preimplantation genetic testing
Preimplantation Genetic Testing
  • Preimplantation Genetic Screening (PGS)
    • Advanced reproductive age
    • Recurrent pregnancy loss
    • Multiple failed IVF cycles
  • Preimplantation Genetic Diagnosis (PGD)
    • Sex-linked disorders (FISH or PCR)
    • Single gene disease
      • Autosomal recessive (PCR)
      • Autosomal dominant (PCR)
    • Translocations (FISH)
slide58
B

A

C

D

E

F

An Atlas of Preimplantation Genetic Diagnosis pg 91

the technology pgs and chromosome translocations

The Technology: PGS and Chromosome Translocations

Alternatives in the near future:

Comparative Genomic Hybridization (CGH)

Multiple Displacement Amplification

Gene Chips

Pyro Sequencing

Fluorescent In-Situ Hybridization (FISH)

trisomy 21 embryo
Trisomy 21 Embryo

Chromosome 21

Chromosome 21

Chromosome 21

An Atlas of Preimplantation Genetic Diagnosis pg 114

when should you refer your patient
When should you refer your patient:
  • You’ve been trying to conceive for > 1year
  • You do not have regular periods
  • You are > 35 years old
  • You have a history of sexually transmitted diseases (i.e. chlamydia)
conclusions
Conclusions
  • Basic Infertility Evaluation
  • Understand the treatment options
  • Understand the complications of treatments
  • We do not know all of the long-term effects of ART because it is still a relatively young field of study.
thank you
THANK YOU

LaTasha B Craig, MD

University of Oklahoma Health

Sciences Center

Section of Reproductive Endocrinology & Infertility

Department of Obstetrics & Gynecology

www.OUInfertility.com

QUESTIONS?

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