Pregnancy WastagePregnancy Wastage

Human reproduction is an inefficient enterprise

Incidence of abortions:

15-20% of clinical pregnancies50-75% of conceptions

Of all pregnant women, how Of all pregnant women, how many will experience an many will experience an abortion?abortion? incidental abortion: 25%

recurrent abortion: 0.5-1.0%

Risk increases: age, parity, smokingRisk decreases: gestational age

“Abortions act as a screening device for abnormal pregnancies”

Clinical types of Clinical types of abortionsabortionsSpontaneous Induced

Septic

Threatened InevitableIncomplete Complete

Missed Blighted Ovum

Intrauterine fetal death Intrauterine fetal death (IUFD)(IUFD)

<20 weeks - spontaneous abortion( missed abortion)

>20 weeks - antepartum fetal death

Management:confirm death

evacuate (D&E, PG, Pitocin)

Recurrent (Habitual) Recurrent (Habitual) AbortionsAbortions

The estimated risk: ?The estimated risk: ? difficulties in the scientific evaluation difficulties in the scientific evaluation of therapies.of therapies.

Number of previousabortions

% of abortions

1 24

2 26

3 32

4 26

Recurrent Abortion Recurrent Abortion Etiology (1)Etiology (1)There are 5 major diagnostic categories:

genetic endocrine anatomic infectious immunologic(A random abortion has, similarly, numerous

possible etiologic causes)

Recurrent Abortion - etiology (2)Recurrent Abortion - etiology (2)

Genetic factors: Translocation - structural rearrangement

in one of the parents - passed to the embryo

Parental balanced translocation:1.9 per 1000 in general population3% in recurrent abortion cases27% with history of both early

abortion & malformed fetus Management: donor oocyte or sperm

Incidence of chromosomal aberrations in sporadic abortions:

50-60% mostly trisomies (16, 22, 21,

18, 13)monosomy x,

triploidy, tetraploidy

Recurrent Abortion - etiology (3)Recurrent Abortion - etiology (3)

Endocrine Factors Corpus luteum dysfunction

luteal progesterone inadequacy

tests: serum progesterone “out of phase” endometrial biopsycauses: Hypothalamic-Pituitary dysfunction

(hyperprolactinemia, nutrition, chronic dis)Management: Progesterone, HCG, clomiphene

(Diabetes M.; Thyroid disorder)

Recurrent Abortion - etiology (4)Recurrent Abortion - etiology (4)

Anatomic factors Congenital: Uterine anomalies DES cervical incompetence Acquired: Intrauterine adhesions

submucous fibroids cervical incompetence Investigation: history, hysteroscopy,

HSGManagement: surgical or “expectant Rx”

Recurrent Abortion - etiology (5)Recurrent Abortion - etiology (5)

Infectious causes: mostly associated with single

abortions

In recurrent abortion: Mycoplasma hominis, U.

Urealyticum ? Tuberculosis ? Bacterial VaginosisManagement: Doxycycline, Erythromycin ?

Recurrent Abortion - etiology (6)Recurrent Abortion - etiology (6)

Immunologic factors Role is undefined and controversial Blocking antibodies are absent or low in

sera of women with recurrent abortions.

Explained by parental sharing of antigens.

Management: (controversial)Immunization of mother with paternal or mixed lymphocytes; IG infusion

Recurrent Abortion - etiology (7)Recurrent Abortion - etiology (7)

More recent findings: Antiphospholipid syndrome

(autoimmune)anticardiolipin antibodieslupus anticoagulants

Activated protein C resistance (genetic)

Clinical features: thrombosis, preg. wastage, complications of pregnancy.Management: Prednisone, Aspirin (mini doze), Heparin, Clexane

Recurrent Abortion - etiology (8)Recurrent Abortion - etiology (8)

Toxic and environmental factors anesthetic gases ? alcohol smoking environmental pollutants

Recurrent Abortion - etiology (9)Recurrent Abortion - etiology (9)

Chronic Disease any chronic disease maternal congenital cardiac disease hypothyroidism (rare cause) diabetes mellitus (advanced dis.) Systemic Lupus Erythematosus

repeated abortionsgenetic(5%)

anatomy(6-12%)

endocrine(15-20%)

infections(5%)

others:APCR

cardiolipin

unexplained50-60%

Preconceptual evaluation of Preconceptual evaluation of couples with recurrent couples with recurrent abortionsabortions remember the main etiologies: genetic,

endocrine, anatomic, immnologic, infectious Diagnostic studies

karyotype of parents

hysterosalpingography, hysteroscopy

APC resistance

anticardiolipin atb, activated PTT,

luteal phase endometrial biopsy?

platelet assessment (for thrombocytosis)

HLA typing, Mixed lymphcyte reaction ?

Thyroid function, Endometrial cultures ?

Early pregnancy Early pregnancy management following management following recurrent abortionsrecurrent abortions

treatments are as yet poorly validated as many as 50 - 75% of pregnancies are

successful even after 3 previous failuresTreatment:

general management guidelines (bed rest, coitus)?

general (HCG, progesterone) specific (surgery, cerclage,

progesterone, steroids, minidoze aspirin, clexane, antibiotics)

Differential Diagnosis of Differential Diagnosis of suspected early pregnany & suspected early pregnany & vaginal bleedingvaginal bleeding early viable & non viable

pregnancy ectopic pregnancy other causes of enlarged uterus

Diagnostic aids: clinical assessment sonography laparoscopy (culdocentesis)

Abortion - Aim of Abortion - Aim of TreatmentTreatment

Uterine evacuation avoidance of infection prevention of Rh sensitization

Evacuation of the uterus - Evacuation of the uterus - technical aspectstechnical aspects “menstrual regulation”

suction curettage sharp curettage cervical dilatation: hegar, laminaria, balloon anesthesia: general, paracervical, sedation mid trimester abortions:

route: intraamniotic or extraamnioticagent: prostaglandins (hypertonic solutions)

antiprogesterone: RU486

Complications of uterine Complications of uterine evacuationevacuation Early

bleeding, coagulation disorders (IUFD) cervical laceration, perforation

Delayedretained products, infection,

bleeding Late

chronic infectioninfertility, ectopic pregnancyRh sensitization

psychological sequelae

ECTOPIC PREGNANCYECTOPIC PREGNANCY

Pregnancy that develops after implantation of the blastocyst anywhere other than the endometrium lining the uterine cavity

Heterotopic preg.: combined intrauterine and extrauterine preg.

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – IncidenceIncidence?

in USA – 1992 – 20/1000 reported preg.

higher rate in older women

& multigravid women

increasing due to:

increased salpingitis

improved diagnostic techniques

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – mortalitymortality

Major cause of maternal death

most common cause in first half of preg. 34 deaths in 1989, USA 4 deaths per 10,000 women with ectopic

(USA, 1989) Cause: blood loss – 88%

infection - 3%

anesthesia complications – 2%

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – etiologyetiology

Infection: major cause of 1st episode; due to morphologic changes

in 40% (1st episode) cause unknown:physiologic: delay of passage of embryo to uterine cavity more than 7 days – when implantation occurs

ovulation from contralateral ovary – uncommonhormonal imbalance (ovulation induction, prog.- releasing IUD) impaired tubal transport

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – tubal pathologytubal pathology

Salpingitis (6 fold increased risk of TP) agglutination of the plicae (folds) of the

endosalpinx sperm passes, but larger morula does not.

Adhesions between tubal serosa and bowel or peritoneum altered tubal motility

Prior ectopic preg. Prior tubal surgery

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – contraception failurecontraception failure

Sterilization failure – 1/3 of pregnancies P only pill – 5% Levonorgestrel (Mirena) releasing IUD Copper IUD

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – pathologypathology

Tubal – 98 %, mostly in the ampullary portion

Abdominal – 1.4%, mostly secondary

Ovarian/cervical - < than 1%

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – pathology (cont.)pathology (cont.)

The morula does not grow mainly in the tubal lumen.

The trophoblast invades the muscularis of the oviduct and grows mainly between the lumen of the tube and its peritoneal covering

Hemorrhage is mainly extraluminal Rupture: the serosa is streched by bleeding,

producing necrosis secondary to an inadequate blood supply

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – pathology, cont.pathology, cont.

Slow growth of trophblastic tissue slow rise of BHCG

Endometrium: secetory – 40%proliferative – 20%decidual – 20%arias stella (endometrial glands

hypertrophied, hyperchromatism, pleomorphism, increased mitotic activity) – 20%

Decidual cast: all the decidua passing through the cervix (DD – abortion)

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – symptomssymptoms

Abdominal pain – nearly universal Amenorrhea Vaginal bleeding Dizziness, fainting

Often, atypical presentation

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – signssigns

Adnexal tenderness Abdominal tenderness Adnexal mass Uterine enlargement Orthostatic changes Fever - uncommon

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – diagnosisdiagnosis

Serial testing

Beta HCGnormal preg. – doubling every 2-3 daysectopic preg. - slow rise

falling levels Progesterone (less than 5 ng/ml)

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – diagnosis (cont.)diagnosis (cont.)

Ultrasoundnormal preg. – at BHCG 1500-2000 mIU/ml

a gestational sac in seenectopic preg. – no IU sac

presence of adnexal mass or gestational sac in oviduct

D&C Culdocentesis Laparoscopy

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – managementmanagement

Surgery: mostly laparoscopicallysalpingectomy, salpingostomysegmental resection

Persistent EP: 5% following salpingostomy Medical Therapy – methotrexate

success: low BHCG - < 5,000 - above 90% > 15,000 – 68%

Expectant management Remember the Rh factor

ECTOPIC PREGNANCY – ECTOPIC PREGNANCY – subsequent conceptionsubsequent conception

Following ectopic – 60%-70% conceive 1/3 ectopic

Higher conception rates (above 80%) following unruptured EP, conservative treatment, no infection

Repeat EP – following 1 EP – 20 % (8% to 27%) following 2 EP – nearly half