Infertility update on evaluation treatment
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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


Ovulation predictor kits

Ovulation Predictor Kits:


Infertility update on evaluation treatment

What to Expect--Fecundability:Cumulative pregnancy rate

Guttmacher, 1956


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.


Infertility update on evaluation treatment

Components of Normal Fertility


Etiologies by percent in couples presenting for infertility

Etiologies by percent in couples presenting for infertility


Male infertility evaluation semen analysis

Male Infertility Evaluation: Semen Analysis


Female infertility evaluation tubal pelvic factor

Female Infertility Evaluation: Tubal/Pelvic Factor


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


Infertility update on evaluation treatment

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.


Infertility update on evaluation treatment

2009 Assisted Reproductive Technology Success Rates, National Summary and Fertility Clinic Reports (CDC)


Infertility update on evaluation treatment

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)


Infertility update on evaluation treatment

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.


Gonadotropins

Gonadotropins


Polycystic ovarian syndrome pcos

Polycystic Ovarian Syndrome (PCOS)


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


Infertility update on evaluation treatment

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

Treatment Options: Unexplained Infertility

See next slide


Infertility update on evaluation treatment

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.


Infertility update on evaluation treatment

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)


Infertility update on evaluation treatment

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


Infertility update on evaluation treatment

IVFLuteal Leuprolide Protocol

Transfer

Retrieval

hCG

2days

3-6days

Gonadotropins8-12 days

Lupron24-30 days

OCPs14-28 days


Infertility update on evaluation treatment

Monitoring FolliclesIVF Ultrasound


Sonographic egg recovery

Sonographic Egg Recovery


Sonographic egg recovery1

Sonographic Egg Recovery


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


Infertility update on evaluation treatment

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.


Embryo transfer

Embryo Transfer


Infertility update on evaluation treatment

Loading Catheter


Embryo transfer1

Embryo Transfer


Outcomes children

Outcomes—Children


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


Infertility update on evaluation treatment

OCTOMOM: Nadya Suleman


Infertility update on evaluation treatment

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)


Infertility update on evaluation treatment

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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