Babies Without a Test-Tube
Dan C. Martin, M.D.
University of Tennessee Health Science Center
Memphis, Tennessee
Babies Without a Test-Tube
www.DanMartinMD.com/bmhwbwtt.htm
Learning Objectives
Following the presentation “Babies With Test
Tube” participants should be able to:
– Understand initial infertility evaluation.
– Clarify evaluation and therapy with:
• Normal History and Physical
• Irregular Menses
• Dysmenorrhea
Patients
• Irregular Menses
• Dysmenorrhea
• Normal History and Physical
Patients
• Irregular Menses  PCOS
• Dysmenorrhea  Endometriosis
• Normal History and Physical
Evaluation
• Months
– 6 Months
– 12 Months
– 36 Months
• Available Resources
• Age
– 28
– 38
– 45
Disclosure
• None
Off-Label Discussion
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•
•
•
Clomiphene Citrate
Oral hypoglycemics
Estradiol
Progestins
Goals
• One healthy baby
• Twins can be a major complication.
• Triplets are often a major complication.
Evaluation
• History
• Physical
• General Lab
– Pregnancy Test, Pap Smear, GC and Chlamydia
– CBC, TSH, prolactin, rubella, vitamin D*
• Fertility Lab
– Semen Analysis
– Luteal Progesterone
* Vitamin D deficiency is associated with pre-eclampsia and C-section for small pelvis
Evaluation
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•
•
•
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Day 3 FSH and E2 if age ≥38 (≥35)
HIV, RPR, fasting glucose, Type and Rh,
free testosterone, testosterone, DHEAS,
17 OHP (follicular)
Sonogram
Sonohysterogram
Hysterosalpingogram (HSG)
Hysteroscopy
Diagnostic Laparoscopy
General
• Prenatal Vitamins
• Pregnancy test before any medication
– Clomiphene Class X
• Includes neural tube defects.
Day 18 to 30 after ovulation
Use folic acid up to 5 mg daily
Start 96 hours to 6 months before pregnant
– Femara Class X
Aging
Windows of Opportunity
Endometrium -Implantation
Ampulla - Fertilization
Cervix (Tube) - Sex
Windows of Opportunity
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•
•
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Cervical sperm survival – 2 to 8 days
Tubal sperm survival – 2 to 8 days?
Ampullary fertilization of egg – 6 to 7 hours
Implantation in endometrium – 6 to 7 days
after LH surge
Windows of Opportunity
• Cervix – 2 to 8 days
Tubal Sperm also?
Estrogenized Tubal Environment
Egg Release
• Ampullary Egg – 6 to 7 hours
• Implantation – 6 to 7 days
Estrogen proliferation and
Progestin maturation of
Endometrium
Estrogenized Cervical Mucus
Basics
• Sperm
• An adequate number of spermatozoa
must be deposited at or near the cervix at
or near the time of ovulation, ascend into
the fallopian tubes, and fertilize an ovum.
Basics
• Ovary
• A mature ovum must be released from
the ovaries, ideally on a regular,
predictable, cyclic basis.
Basics
• Cervix
• The cervix must capture, nurture, and
release spermatozoa into the uterus that
then travel into the fallopian tubes.
Basics
• Peritoneum
• The fallopian tubes must have a
functional anatomic relationship with the
adjacent ovaries to facilitate travel and
capture.
Basics
• Tubes
• The fallopian tubes must be patent and
also capable of timely transport of an
embryo to the uterine cavity.
Basics
• Uterus
• The uterus must be receptive to embryo
implantation and capable of supporting
subsequent normal growth and
development.
Ovulation Predictor Kits
Ovulation
• An LH (luteinizing hormone) surge begins 24 to 36
hours prior to ovulation and peaks 12 to 24 hours
before ovulation.
• Follicular rupture = It is the ovary’s job to make a
cyst and rupture it.
• Progesterone is increasingly produced after the LH
surge
• Secretory changes occur in the endometrium due to
progesterone.
Ovulation
• Pregnancy is absolute proof of ovulation.
• Serum progesterones are 99%+
– 8 days after a positive ovulation test
– 7 days after ovulation on a monitor
– Day 21 and 24 if ovulation day is uncertain.
Patients
• Irregular Menses
• Dysmenorrhea
• Normal History and Physical
Ovulation Disorders
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•
•
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PCOS
Hypothyroidism
Hyperprolactinemia
Weight Loss / Weight Gain
PCOS
PCOS
• Diagnosis is more clinical than lab.
– Androgenism (hirsute, acne, central obesity)
– Oligo-anovulatory
– PCOM – polycystic morphology
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•
•
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> 12 follicles at 2 - 9 mm in at least 1 ovary
Volume > 10cc
Does not apply if on BCPs
If a follicle is >10mm, repeat scan next cycle
– Elevated androgens
• Androgens decrease with age
– Decreased HDL and SHBG
PCOS
• Treatment
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–
–
–
Weight loss and exercise
Clomid (clomiphene citrate) (3 months)
Femara (aromatase inhibitor) (3 months)
Metformin (6 months)
• Note that the combination of Metformin and
Clomid are more productive at months 4-6
compared with months 1-3 .
– Gonadotropins
PCOS
• Weight loss
– Poor results if BMI > 50
– Requires a dedicated program of diet and
exercise
– Use dieticians who work with diabetics
– Liposuction of cutaneous fat is not the same
as loss of visceral weight
Yee 2003
Letrozole and Clomiphene
Birth Defects
• There is no increase in birth defects for
letrozole or clomiphene if used when not
pregnant.
• Letrozole associated with fewer birth
defects than clomiphene but this is not
statistically significant.
Tulandi T. Fertil Steril 85:1761, 2006
Clomiphene
• Four ovarian responses to clomiphene
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–
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Ovulatory response
Anovulatory response
Ovulatory dysfunction
Luteinized unruptured follicle (LUF)
• Ultrasound characteristics of ovulation
Ovulation Monitoring
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•
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Basal body temperature charting (BBTC)
Mid luteal phase serum progesterone
Urine LH hormone detection (ovulation kits)
Serial ultrasounds for follicular growth and
collapse.
Sonographic Collapse
• Collapse at 24 mm maximum
or 21 mm mean with no stimulation –
2 to 3 mm larger with clomiphene
• Scan 1 to 2 days after collapse
Luteinized Unruptured Follicle
• No Collapse
• May respond to 10,000 to 20,000 IU HCG
Clomiphene Citrate
for PCOS
• Ovulatory rate - 80%
• Pregnancy rate - 40%
• Multiple rate
– Twins - 5%
– Triplets - < 1%
• 80% of pregnancies occur in 4 cycles
– 85% at 3 months if IUI
Patients
• Irregular Menses
• Dysmenorrhea
• Normal History and Physical
Endometriosis
Minimum
Theoretical
1%
Family Practice 1%
Gyn Practice
30%
Maximum
99%
15%
72%
Powder Burn?
1) Infiltrating dark and scarred or
2) Surface vesicles and hemosiderin.
These lesions have different histology
and behavior.
Theories
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•
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Retrograde Menstruation - Implantation
Mullerian Tissue Present at Birth
Coelomic Metaplasia
Vascular Metastasis
Lymphatic Metastasis
Theories
Implantation
Nisolle 1997
Nisolle 1997
Theories
• Retrograde Menstruation
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Pelvis
Bowel
Bladder
Appendix
Vagina
Sciatic Nerve
Diaphragm (Lungs)
Natural Progression
if Progressing
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Implantation
Clear Blisters
Red Polypoid Blisters
Scarring and Blood Trapping
Collection of Old Blood
More Scar
Deep Infiltration
Histological Diagnosis
Histological Diagnosis
Histological Diagnosis
Glandular Epithelium 
Old Blood 
Stroma 
Fibromuscular Scar 
Pelvic Adhesions
• Terminology
No consistent definitions
– Dense or Filmy
– Thick or Thin
– Opaque or Translucent
– Vascular or Avascular.
Normal Anatomy
Filmy Adhesions
Fitz-Hugh Curtis Adhesions
Curtis 1930 and Fitz-Hugh 1934
Dense and Filmy Adhesions
Patients
• Irregular Menses
• Dysmenorrhea
• Normal History and Physical
Options
• Evaluate and Treat Specific Problems
– PCO
– Prolactinemia, etc
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•
•
•
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Clomiphene
IUI
Clomiphene IUI
Empirical Trials
hMG IUI
•
Assisted Reproductive Technologies
These are not today’s subject since few of my patients can afford them.
Marcoux NEJM 337:217, 1997
Marcoux NEJM 337:217, 1997
Pregnancy After Laparoscopy
Comparative
cumulative pregnancy
curves using the twoparameter exponential
model for stage I and
II endometriosis
patients with no other
infertility factors.
Olive Fertil Steril 1987
Guzick Fertil Steril 1983
36 Weeks
36 Months
Empirical Clomiphene
3 Month Fecundability
Monthly
6.8%  8.7%
1%  3.38%
Empirical Clomiphene
3 Month Fecundability
• Monthly
– 6.8%  8.7%
– 1%  3.38%
• Walgreens 3 months for $12
– $ 114 to $303 per baby
Babies Without a Test-Tube
www.DanMartinMD.com/bmhwbwtt.htm