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Infertility 101
Laura L. Tatpati, MD
Division of Reproductive Endocrinology & Infertility
Department of Obstetrics and Gynecology
University of Kansas School of Medicine - Wichita
No disclosures
Objectives
Understand key historical and clinical findings which can aid in
assessment of gynecologic conditions which affect fertility
Review diagnostic testing options and their appropriate usage
Understand how to utilize these for enhanced efficiency/efficacy of
treatment of the patient
Infertility
A disease defined by the failure to achieve a
successful pregnancy after 12 months or more of
appropriate, timed unprotected intercourse or
therapeutic donor insemination
Early evaluation and treatment:
Medical history and physical findings
After 6 months if female partner is > 35 y
http://dx.doi.org/10.1016/j.fertnstert.2012.09.023
Fertility
80% will conceive w/in 6 mo
Monthly fecundibility is highest in the 1st
3 mo
Relative fertility is about ½ for women in
their late 30s vs. early 20s
http://dx.doi.org/10.1016/j.fertnstert.2013.07.011
Peritoneal Factors
Tubal
Factors
Ovulatory
Factors
Uterine
Factors
Cervical
Factors
ASRM : Optimal Evaluation of the Infertile Female, 2012
The History
History is essential
Menarche
Periods…everything you ever wanted to know
Ovulation/pre-menstrual symptoms
Pregnancy history / how long TTC?
Contraception history
Coital frequency/dyspareunia/lubricants
Q 1-2d
Hydroxyethylcellulose-based, canola or mineral oil
STIs
Pap smears/mammogram
Patient Goals and methods they’ve tried
Goals:
When do they want to
conceive?
How many children are
they considering?
Methods:
Temperature charting
Ovulation testing
Method for timing of
intercourse
Other medical interventions
General Medical History
Current diseases
Chronic diseases
Medications & herbal preparations
Allergies
Surgeries
ROS
Headaches
Vision problems
Breast discharge
Hair growth
Acne
Thyroid disease sx
Dyspareunia
Pelvic pain
Bowel/bladder complaints
Family history
DM, CAD, HTN
Cancer: breast, ovarian, uterine, colon, thyroid, pancreatic
Other diseases in family
Infertility issues, RPL
Birth defects
Learning delay, Autism, MR
Social history
Tobacco, EtOH, drugs
Tobacco 40% reduction in
IVF LBR
Moderate alcohol 1-2/d
Mixed data
500mg caffeine daily
Occupation
Exercise
Exam
Vitals (BP, BMI)
HEENT
Skin
CV/Lungs
Breasts
Abdomen
Pelvic
Case Study
31 yo G1P1001
3 year history of infertility
She reached menarche at age 12
She had a term delivery at age 18
Menses “like clock-work”
No premenstrual symptoms
She has acne and denies having any problems with excessive
hair growth
Ovulatory factors
Up to 40% of female factor infertility
Can be subtle dysfunction
Underlying condition should be sought due to
risk for health implications
Evaluating ovulation
Likely ovulatory if:
q 25-35d
Moliminal sx
Consistent flow
< about 45 years old
Testing for ovulation
BBT
Abnormal if:
Monophasic
<10d luteal phase temp elevation
Limitations
Less reliable for defining ovulation timing
Occ ovulatory w/ mono-phasic
Peak fertile about 7d prior
Luciano. Obstet Gynecol 1990; 75: 412-6
Mid-Luteal serum progesterone
>3ng/ml – presumptive
Mid-luteal is a retrospective diagnosis!
Urinary LH kits
Indirect evidence
Likely ovulation in 1-2d
Most reliable for ovulation prediction
Testing for ovulation cont.
Endometrial biopsy
>2 days
Lacks accuracy and precision
Cannot distinguish fertile/infertile
Should be utilized for those in whom abnormal
pathology is a concern (neoplasia or chronic
endometritis)
TVUS
Costly
Reserved for those that simpler methods are
ineffective for (primarily used in treatment)
Diagnosis of Ovulatory factors
Lab evaluation
TSH
Prolactin
FSH/E2 (any day if amenorrheic, day 3 if cyclic)
Ovarian failure, hypothalamic dysfunction (LH if
this is a concern), diminished ovarian reserve
Clomid challenge test
Testosterone
?AMH
Clinical suspicions of ovulatory
dysfunction
History, History, History
Pubertal disturbances
Menstrual history
Secondary oligo- or amenorrhea
Pregnant #1
Ovarian disease — 40 percent
Hypothalamic dysfunction — 35 percent
Pituitary disease — 19 percent
Uterine disease — 5 percent
Other — 1 percent
Diagnostic approach to secondary amenorrhea
©2007 UpToDate® • www.uptodate.com
Licensed to Mayo Foundation
Treatment of Ovulatory Factors:
PCOS
If obesity related –
First-line treatment is diet modification and
exercise
May proceed with inexpensive treatment modalities (CC +/IUI)
3-6 cycles w/o success indicates need for
complete evaluation
SA if oligo rather than amenorrhea
6 mo LBR 20–40%
½ who do conceive do so on 50mg, 20% on 100mg
10% risk of twins, 0.5% risk of triplets or more
What about metformin?
CC 3x as effective
Metformin is not recommended as 1st line agent
Alone – 1-2 additional ovulatory events / yr
Adding metformin to clomiphene may enhance PR in
obese patients
OR, 2.67; 95% CI, 1.45–4.94; NNT 4.6
Creanga. Obstet Gynecol 2008;111:959–68.
Treatment of Ovulatory Factors:
Other endocrine/hypothalamic
Other endocrine disorders
Treat this first
Hypogonadotrophic Hypogonadism
Gonadotropins (hCG/FSH likely best)
IVF
The Age Issue
ASRM Practice Committee. Optimizing natural fertility. Fertil Steril 2008
Dx of Ovulatory Factor:
DOR/POF/AMA
Ovarian reserve testing
>35
FH early menopause
Single ovary or hx ovarian surgery
Chemotherapy or pelvic radiation therapy
Unexplained infertility
Prior poor response to gonadotropins
Planning ART
Dx of Ovulatory Factor:
DOR/POF/AMA
FSH > 10-15, AFC <5 (?3), AMH < 1??
Gonadotropins vs IVF vs Egg donation
Age is independent variable
>42 = < 5% chance success with non-donor IVF
Consider REI referral
Peritoneal Factors
Tubal
Factors
Ovulatory
Factors
Uterine
Factors
Cervical
Factors
ASRM : Optimal Evaluation of the Infertile Female, 2012
Uterine factors
Relatively uncommon cause of
infertility
Malformation
Synechiae
Polyps
Myomata
Pelvic radiation
Cervical - ? Chronic cervicitis
Tubal Factor: Diagnosis
History
Tubal ligation
Ectopic/Torsion
Ovarian surgery or oophorectomy
STDs or PID
Hx Complicated Appendectomy/Bowel surgery
Uterine/Tubal Evaluation
Methods of evaluation
HSG
Ultrasound/3D US
Sonohysterography
Hysteroscopy - definitive
Reserved for further evaluation/treatment or
If laparoscopy planned for evaluation
Endometriosis or Pelvic adhesions
Diagnosis
Suspicious history or prior diagnosis
Suspect if diagnostic tests are negative or negligible
Infertility vs Tubal ligation at laparoscopy
38% vs 5%
1/3 w/endometriosis - asymptomatic
Ultrasound: endometriomas, fluid collections
Laparoscopy: definitive
Laparoscopy to Enhance Fertility
Benefits with advanced endometriosis
Unclear with early stage disease
2 RCTs
Canadian collaborative trial
29% vs 17% PR > 20wks (Tx vs No Tx)
Italian study
20% vs 22% LBR after 1 yr (Tx vs No Tx)
Combined
NNT 12 (CI 7-49)
New patient
24 yo female, regular cycles
No dysmenorrhea, acne, hirsutism
Nothing concerning in history
Completed 9 cycles of clomid
Had one ER visit for pain after ovulation in
4th cycle
Normal HSG
What about him?
Male factor
13%
5%
Ovulatory
14%
20%
Tubal
Peritoneal
Uterine/Cervical
18%
Male
Unexplained
30%
Additional 30-50% likely due to
combined factors
I’m good.
Things to watch for…
His “mom” had some trouble getting pregnant,
but had 2 children 4 years apart
Healthy, goes to the gym daily for 1-2 hrs daily
No smoking (but does he chew???)
Goes out w/ buddies on weekends
“I only drink during KU games”
Had to see Dr. for varicocele, but didn’t change,
so left alone
Had some kind of “hernia” repaired as an infant,
but I don’t know details…
Male Factor Evaluation
Current Physical
Hernias, varicoceles
BMI
Elevated
Increased estrogen levels, feedback to LH, decr
testosterone?
Decreased Counts
Reduced (acute/chronic illness)
Decrease GnRH
Male Factor Evaluation
Semen Analysis
2-3 days abstinence
>7 days – senescence/debris
X 2 (1 month apart)
Reference values are not minimum values
needed & normal values do not prove male is
fertile
Semen Analysis
Volume 1.5-5ml
Count (Concentration) - >20 million/mL and
Motility >50%
>5M TMC for inseminations
Also, morphology, WBC, agglutination
Male Factor Infertility Treatments
GnRH pump
FSH/LH
Clomiphene
Sperm banking
Donor sperm
Testicular aspiration/biopsy (MESA/TESE)
ICSI w/ IVF
Conclusion
Complete history for both partners
Think in stepwise fashion
Initiate testing per history
Don’t forget 30-40% risk of combined infertility
Referral to REI &/or Urologist as clinically indicated
Questions?
References
ASRM. Practice Committee Report. Optimal evaluation
of the Infertile Female.
Doi:10.1016/j.fertnstert.2012.05.032
AUA and ASRM. Report on Optimal Evaluation of the
Infertile Male. 2001
Optimizing Natural Fertility.
http://dx.doi.org/10.1016/j.fertnstert.2013.07.011
ACOG. Polycystic Ovarian Syndrome. Clinical
Management Guidelines for Obstetrician-Gynecologists.
Number 108, October 2009
References
Marcoux S, Maheux R, Berube S. Laparoscopic surgery in
infertile women with minimal or mild endometriosis.
Canadian Collaborative Group on Endometriosis. N Engl
J Med 1997 Jul 24;337(4):217-22.