risk of recurrent pregnancy loss. introduction emotionally traumatic, similar to stillbirth or...

40
RISK OF RECURRENT PREGNANCY LOSS

Upload: ruth-norman

Post on 17-Jan-2016

226 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

RISK OF RECURRENT PREGNANCY LOSS

Page 2: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

INTRODUCTION 

Emotionally traumatic, similar to stillbirth or neonatal death

Etiology is often unknown Primary or secondary

Live birth occurred at some time in secondary Better prognosis with secondary

Page 3: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

DEFINITION 

≥ 3 consecutive losses of clinically recognized pregnancies < 20 week gestationEctopic, molar, and biochemical pregnancies not included

15 % experience sporadic loss of clinically recognized pregnancy

2 % experience 2 consecutive losses0.15 x 0.15 = 0.0225 = 2 %

0.4 to 1 % experience 3 consecutive losses 0.15 x 0.15 x 0.15 = 0.003 = 0.3 % observed frequency is

higher than expected by chance alone

Page 4: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

RISK FACTORS AND ETIOLOGY

Only in 50 %, the cause can be determined Etiological categories:

UterineImmunologicEndocrineGeneticThrombophilicEnvironmental

Page 5: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

UTERINE FACTORS

Acquired or congenital anomalies Congenital anomalies: 10 -15 % in ♀ with

RPL vs. 7 % in all ♀ Abnormal implantation:

↓ vascularity (septum)↑ inflammation (fibroid)↓ sensitivity to steroid hormones

Page 6: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

SEPTATE UTERUS

Most common Poorest outcome Miscarriage > 60 % Fetal survival with untreated cases 6 to 28 % The longer, the worse The mechanism

Not clearly understoodPoor blood supply poor implantation

Page 7: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

LEIOMYOMA

Submucous The mechanism

Their positionPoor endometrial receptivityDegeneration with increasing cytokine

production

Page 8: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

OTHER UTERINE CAUSES

Endometrial polypsRx: Polypectomy

Intrauterine adhesionsCurettage for pregnancy complications (4/52)Traumatize basalis layer granulation tissueInsufficient endometrium to support

fetoplacental growth Menstrual irregularities (hypomenorrhea,

amenorrhea), cyclic pelvic pain, infertility.

Page 9: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

OTHER UTERINE CAUSES

Cervical insufficiencyRecurrent mid-trimester loss

Other uterine anomaliesImpaired uterine distention

Page 10: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

IMMUNOLOGIC FACTORS

Antiphospholipid syndrome (APAS)5 - 15 % of ♀ with RPL may have APAS

Other immunological factorsNot well defined

Page 11: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

ENDOCRINE FACTORS

Luteal phase defectProgesterone is essential for implantation and

maintenance of pregnancy○ A defect in C.L. impaired progesterone

productionControversies:

○ Does this defect really exists?○ If it does, is related to miscarriage?○ No consensus on method of diagnosis○ No consensus on method of treatment

Page 12: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

ENDOCRINE FACTORS

Diabetes mellitusPoorly controlled early (and late) loss

○ No ↑ risk with well-controlled Mechanism

○ Hyperglycemia○ Maternal vascular disease○ Immunologic factors (possible)

Page 13: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

ENDOCRINE FACTORS

Insulin resistance No strong evidencePCOS

○ Miscarriage 20 - 40% vs. baseline rate 10 - 20%Mechanism is unknown

○ ↑ LH, Testosterone, and androstenedione adversely affect the endometrium

Page 14: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

ENDOCRINE FACTORS

Thyroid disease and antibodiesPoorly controlled hypo- or hyper-thyroidism

○ Infertility & pregnancy loss ↑ thyroid antibody, even if euthyroid.

○ No strong evidence

HyperprolactinemiaRx ↑ successful pregnancy (86 vs. 52%)BUT, need correct diagnosisAt what level to treat?

Page 15: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

GENETIC FACTORS 

↑ RPL in 1st degree relatives of ♀ with unexplained RPLShared HLA types, coagulation defects, immune

dysfunction, other undefined heritable factors Chromosomal rearrangements

5 % of couples with RPL have major chromosomal defects (vs. 0.7 %)○ Balanced translocation or an inversion

Even if present, may not be the cause complete evaluation of RPL is indicated

Page 16: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

THROMBOPHILIA

Thrombosis on maternal side of the placenta impair placental perfusionLate fetal loss, IUGR, abruption, or PIH

Relationship with early loss is less clearlarge and contradictory literature May be restricted to specific defects not

completely defined, or presence of multiple defects

Page 17: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

MISCELLANEOUS Environmental chemicals & stress

Anesthetic gases (nitrous oxide), formaldehyde, pesticides, lead, mercury○ Sporadic spontaneous loss ○ No evidence of associations with RPL

Personal habits Obesity, smoking, alcohol, and caffeine

○ Association with RPL is unclearMay act in a dose-dependent fashion or synergistically to

↑ sporadic pregnancy loss Exercise

does not ↑ sporadic or RPL

Page 18: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

MISCELLANEOUS Male factor

Trend toward repeated miscarriages with abnormal sperm (< 4% normal forms, sperm chromosome aneuploidy) ○ ICSI

Paternal HLA sharing not risk factor for RPLAdvanced paternal age may be a risk factor for

miscarriage (at more advanced age than females) Infection

Listeria, Toxoplasma, CMV, and primary genital herpes

Cause sporadic loss, but not RPL

Page 19: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

MISCELLANEOUS

Decreased ovarian reserveQuality and quantity of oocytes decrease♀ with unexplained RPL have a higher D3 FSH

and E2 than ♀ with known cause Celiac disease

Untreated & even subclinical, associated with pregnancy loss, menstrual disorders, and infertilityTreatment prevent these problems

No evidence that it causes RPL

Page 20: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

CANDIDATES FOR EVALUATION 

Evaluate and Rx ≥ 2 or 3 consecutive losses Most have good prognosis for a successful

pregnancy, even when no Dx or Rx The minimum workup:

Complete medical, surgical, genetic, and family history

Physical examination

Page 21: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

HISTORY 

GA & characteristics (anembryonic pregnancy, live embryo) of all previous pregnanciesRPL typically occurs at a similar GAMost common causes of RPL vary by trimester

○ Chromosomal & endocrine earlier than anatomic or immunological causes

Uterine instrumentation intrauterine adhesions Menstrual cycles regularity endocrine

dysfunction Galactorrhea, Headache, Visual disturbances

hyperprolactinemia

Page 22: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

HISTORY 

Thyroid related symptoms Hx of congenital or karyotypic abnormalities

heritable Was cardiac activity detected? If not suggests

chromosomal abnormality Does F.Hx display patterns of disease consistent with

strong genetic influence? consanguinity Exposure to environmental toxins Hx venous thrombosis thrombophilia or APAS Information from previous laboratory, pathology, and

imaging studies

Page 23: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

PHYSICAL EXAMINATION

General physical Signs of endocrinopathy (hirsutism,

galactorrhea, thyroid) Pelvic organ abnormalities (uterine

malformation, cervical laceration)

Page 24: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

LABORATORY EVALUATION 

Karyotype (Parental)Low yield & limited prognostic value only if

the other work-up was negative Karyotype (Embryonic)

Not really neededMay consider after 2nd lossIf abnormal karyotype + normal parents “bad

luck”

Page 25: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

UTERINE ASSESSMENT Sonohysterography (SIS)

More accurate than HSG Differentiate septate & bicornuate uterus

Hysterosalpingogram (HSG)Does not evaluate outer contourNot ideal for the cavity

HysteroscopyGold standard for Dx + Rx intrauterine lesionsCannot differentiate septate from bicornuateReserved for when no Dx is made

Page 26: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

UTERINE ASSESSMENT

UltrasoundPresence and location of uterine myomas Associated renal abnormalities

MRIDifferentiate septate from bicornuate

Hysteroscopy, laparoscopy, or MRI second-line tests when additional information is required

Page 27: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

APAS Dx: one lab & one clinical criteria are met Clinical criteria:

Venous or arterial thrmobosisRPL

Laboratory criteriaLupus anticoagulantAnticardiolipin antibody (IgG and IgM)

Medium or high titers of bothLow to mid positive can be due to viral illness

Repeat twice, 6-8 weeks apart

Page 28: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

THROMBOPHILIA

Contradictory literature Evaluate if loss > nine weeks + evidence of

placental infarction or maternal thrombosis

Page 29: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

THYROID

TSH +/- FT4 & FT3More important in ♀ with clinical manifestations

but even in asymptomatic Thyroid peroxidase antibody

Page 30: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

OVARIAN RESERVE

D3 FSH +/- D3 E2 in ♀ of any age or ¼ would be missed

Clomiphene challenge test

Page 31: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

NONE USEFUL TESTS

Routine cervical cultures for Chlamydia, Mycoplasma & vaginal evaluation for BV & toxoplasmosis serology

ANA Screening for DM Immune function (HLA typing, etc) Progesterone level (Single or multiple) Endometrial biopsy

Page 32: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

MANAGEMENT

Prognosis for successful future pregnancy is goodlive birth rates after normal and abnormal

diagnostic evaluations, 77 and 71 percent, respectively

Emotional support is important and enhance success

Page 33: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

PARENTAL KARYOTYPE ABNORMALITY

Refer for genetic counselingInformation for probability of a chromosomally

normal or abnormal conception May undergo prenatal genetic studies

AmniocentesisCVSIVF with PGD

Page 34: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

UTERINE ABNORMALITIES

Managed hysteroscopically Septum, adhesions, submucosal myoma

Cervical cerclage Second trimester loses

Page 35: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

MANAGEMENT Antiphospholipid syndrome

Aspirin & Heparin Suspected immunologic dysfunction 

Several immunologic Rx advocatedNone effectiveSome are harmful

DMControlled at least 6/12 prior to conception

ThyroidHyper and Hypo thyroid should be controlledEuthyroid with ↑ peroxidase antibody may benefit

from treatment

Page 36: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

MANAGEMENT

Polycystic ovary syndrome No agreed upon protocolMetformin just as effective when stopped at

diagnosis of pregnancy or 12/52 gestation Hyperprolactinemia 

Normal levels play important role in maintaining early pregnancy (in RPL)

Thrombophilia Anticoagulation if loss > 9/52

Page 37: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

UNEXPLAINED RPL 

50% of RPL remain unexplained Prognosis is still good

>50 % live birth even without intervention

Page 38: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

UNEXPLAINED RPL 

Lifestyle modification Eliminating use of tobacco, alcohol, and caffeine

& reduction in BMI (for obese women). Progesterone

Widely used but studies on its efficacy are lackingVaginally or IM

Human menopausal gonadotropinCorrecting LPD or creating thicker endometriumClinical experience supports the efficacy

IVF +/- PGDMixed resultsPromising

Page 39: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

UNEXPLAINED RPL 

Useless interventions:hCGCC

Pregnancy issues Increased risk of :

○ IUGR○ PTD

No increased risk of:○ PIH○ GDM

Page 40: RISK OF RECURRENT PREGNANCY LOSS. INTRODUCTION  Emotionally traumatic, similar to stillbirth or neonatal death  Etiology is often unknown  Primary

Thank you