Babies Without a Test-Tube DanMartinMD/bmhwbwtt.htm
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Transcript of Babies Without a Test-Tube DanMartinMD/bmhwbwtt.htm
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Babies Without a Test-TubeBabies Without a Test-Tube
Dan C. Martin, M.D.Dan C. Martin, M.D.
University of Tennessee Health Science CenterUniversity of Tennessee Health Science CenterMemphis, TennesseeMemphis, Tennessee
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Babies Without a Test-TubeBabies Without a Test-Tube
www.www.DanMartinMD.com/bmhwbwtt.htmDanMartinMD.com/bmhwbwtt.htm
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Learning ObjectivesLearning 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
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PatientsPatients
• Irregular Menses
• Dysmenorrhea
• Normal History and Physical
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PatientsPatients
• Irregular Menses PCOS
• Dysmenorrhea Endometriosis
• Normal History and Physical
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EvaluationEvaluation
• Months– 6 Months– 12 Months– 36 Months
• Available Resources
• Age– 28– 38– 45
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DisclosureDisclosure
• None
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Off-Label DiscussionOff-Label Discussion
• Clomiphene Citrate
• Oral hypoglycemics
• Estradiol
• Progestins
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GoalsGoals
• One healthy baby• Twins can be a major complication.• Triplets are often a major complication.
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EvaluationEvaluation
• 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
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EvaluationEvaluation
• 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
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GeneralGeneral
• Prenatal Vitamins• Pregnancy test before any medication
– Clomiphene Class X• Includes neural tube defects.
Day 18 to 30 after ovulationUse folic acid up to 5 mg dailyStart 96 hours to 6 months before pregnant
– Femara Class X
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AgingAging
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Windows of OpportunityWindows of Opportunity
Cervix (Tube) - Sex
Ampulla - Fertilization
Endometrium -Implantation
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Windows of OpportunityWindows of Opportunity
• 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
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Windows of OpportunityWindows of Opportunity• Cervix – 2 to 8 days
Tubal Sperm also?
• Ampullary Egg – 6 to 7 hours
• Implantation – 6 to 7 days
Estrogenized Tubal Environment
Egg Release
Estrogen proliferation and
Progestin maturation of
Endometrium
Estrogenized Cervical Mucus
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BasicsBasics
• 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.
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BasicsBasics
• Ovary
• A mature ovum must be released from the ovaries, ideally on a regular, predictable, cyclic basis.
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BasicsBasics
• Cervix
• The cervix must capture, nurture, and release spermatozoa into the uterus that then travel into the fallopian tubes.
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BasicsBasics
• Peritoneum
• The fallopian tubes must have a functional anatomic relationship with the adjacent ovaries to facilitate travel and capture.
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BasicsBasics
• Tubes
• The fallopian tubes must be patent and also capable of timely transport of an embryo to the uterine cavity.
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BasicsBasics
• Uterus
• The uterus must be receptive to embryo implantation and capable of supporting subsequent normal growth and development.
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Ovulation Predictor KitsOvulation Predictor Kits
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OvulationOvulation
• 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.
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OvulationOvulation
• 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.
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PatientsPatients
• Irregular Menses
• Dysmenorrhea
• Normal History and Physical
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Ovulation DisordersOvulation Disorders
• PCOS
• Hypothyroidism
• Hyperprolactinemia
• Weight Loss / Weight Gain
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PCOSPCOS
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PCOSPCOS• Diagnosis is more clinical than lab.
– Androgenism (hirsute, acne, central obesity)
– Oligo-anovulatory
– PCOM – polycystic morphology• > 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
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PCOSPCOS
• Treatment– 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
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PCOSPCOS
• 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
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Yee 2003
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Letrozole and ClomipheneLetrozole and ClomipheneBirth DefectsBirth 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
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ClomipheneClomiphene
• Four ovarian responses to clomiphene– Ovulatory response– Anovulatory response– Ovulatory dysfunction– Luteinized unruptured follicle (LUF)
• Ultrasound characteristics of ovulation
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Ovulation MonitoringOvulation Monitoring
• Basal body temperature charting (BBTC)• Mid luteal phase serum progesterone• Urine LH hormone detection (ovulation kits)• Serial ultrasounds for follicular growth and
collapse.
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Sonographic CollapseSonographic 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
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Luteinized Unruptured FollicleLuteinized Unruptured Follicle
• No Collapse
• May respond to 10,000 to 20,000 IU HCG
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Clomiphene CitrateClomiphene Citratefor PCOSfor 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
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PatientsPatients
• Irregular Menses
• Dysmenorrhea
• Normal History and Physical
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EndometriosisEndometriosis
Minimum Maximum
Theoretical 1% 99%
Family Practice 1% 15%
Gyn Practice 30% 72%
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Powder Burn?Powder Burn?
1) Infiltrating dark and scarred or
2) Surface vesicles and hemosiderin.
These lesions have different histology and behavior.
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TheoriesTheories
• Retrograde Menstruation - Implantation
• Mullerian Tissue Present at Birth
• Coelomic Metaplasia
• Vascular Metastasis
• Lymphatic Metastasis
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TheoriesTheoriesImplantation
Nisolle 1997
Nisolle 1997
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TheoriesTheories• Retrograde Menstruation
– Pelvis
– Bowel
– Bladder
– Appendix
– Vagina
– Sciatic Nerve
– Diaphragm (Lungs)
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Natural ProgressionNatural Progressioni f P r o g r e s s i n gi f P r o g r e s s i n g
• Implantation• Clear Blisters• Red Polypoid Blisters• Scarring and Blood Trapping• Collection of Old Blood• More Scar• Deep Infiltration
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Histological DiagnosisHistological Diagnosis
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Histological DiagnosisHistological Diagnosis
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Histological DiagnosisHistological Diagnosis
Fibromuscular Scar
Stroma
Glandular Epithelium Old Blood
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Pelvic AdhesionsPelvic Adhesions
• TerminologyNo consistent definitions– Dense or Filmy– Thick or Thin– Opaque or Translucent– Vascular or Avascular.
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Normal AnatomyNormal Anatomy
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Filmy AdhesionsFilmy Adhesions
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Fitz-Hugh Curtis AdhesionsFitz-Hugh Curtis Adhesions
Curtis 1930 and Fitz-Hugh 1934
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Dense and Filmy AdhesionsDense and Filmy Adhesions
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PatientsPatients
• Irregular Menses
• Dysmenorrhea
• Normal History and Physical
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OptionsOptions
• Evaluate and Treat Specific Problems– PCO– Prolactinemia, etc
• 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.
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Marcoux NEJM 337:217, 1997Marcoux NEJM 337:217, 1997
Marcoux NEJM 337:217, 1997
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Pregnancy After LaparoscopyPregnancy After Laparoscopy
Comparative cumulative pregnancy curves using the two-parameter exponential model for stage I and II endometriosis patients with no other infertility factors. Olive Fertil Steril 1987
Guzick Fertil Steril 198336 Weeks 36 Months
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Empirical ClomipheneEmpirical Clomiphene3 Month Fecundability3 Month Fecundability
Monthly6.8% 8.7%1% 3.38%
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Empirical ClomipheneEmpirical Clomiphene3 Month Fecundability3 Month Fecundability
• Monthly– 6.8% 8.7%– 1% 3.38%
• Walgreens 3 months for $12– $ 114 to $303 per baby
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Babies Without a Test-TubeBabies Without a Test-Tube
www.www.DanMartinMD.com/bmhwbwtt.htmDanMartinMD.com/bmhwbwtt.htm