Pregnancy Wastage l Human reproduction is an inefficient enterprise l Incidence of abortions: 15-20% of clinical pregnancies 50-75% of conceptions

Of all pregnant women, how many will experience an abortion? l incidental abortion: 25% l recurrent abortion: % Risk increases: age, parity, smoking Risk decreases: gestational age “Abortions act as a screening device for abnormal pregnancies”

Clinical types of abortions SpontaneousInducedSeptic ThreatenedInevitable IncompleteComplete Missed Blighted Ovum

Intrauterine fetal death (IUFD) l < 20 weeks - spontaneous abortion (missed abortion) l > 20 weeks - antepartum fetal death Management: confirm death evacuate (D&E, PG, Pitocin)

Recurrent (Habitual) Abortions The estimated risk: ? difficulties in the scientific evaluation of therapies. Recurrent (Habitual) Abortions The estimated risk: ? difficulties in the scientific evaluation of therapies.

Recurrent Abortion Etiology (1) There are 5 major diagnostic categories: l genetic l endocrine l anatomic l infectious l immunologic (A random abortion has, similarly, numerous possible etiologic causes)

Recurrent Abortion - etiology (2) Genetic factors: l Translocation - structural rearrangement in one of the parents - passed to the embryo l Parental balanced translocation: 1.9 per 1000 in general population 3% in recurrent abortion cases 27% with history of both early abortion & malformed fetus l Management: donor oocyte or sperm

l Incidence of chromosomal aberrations in sporadic abortions : 50-60% mostly trisomies (16, 22, 21, 18, 13) monosomy x, triploidy, tetraploidy

Recurrent Abortion - etiology (3) Endocrine Factors l Corpus luteum dysfunction luteal progesterone inadequacy tests: serum progesterone “out of phase” endometrial biopsy causes: Hypothalamic-Pituitary dysfunction (hyperprolactinemia, nutrition, chronic dis) Management: Progesterone, HCG, clomiphene l (Diabetes M.; Thyroid disorder)

Recurrent Abortion - etiology (4) Anatomic factors l Congenital: Uterine anomalies DES cervical incompetence l Acquired: Intrauterine adhesions submucous fibroids cervical incompetence l Investigation: history, hysteroscopy, HSG Management: surgical or “expectant Rx”

Recurrent Abortion - etiology (5) Infectious causes: l mostly associated with single abortions In recurrent abortion: l Mycoplasma hominis, U. Urealyticum ? l Tuberculosis ? l Bacterial Vaginosis Management: l Doxycycline, Erythromycin ?

Recurrent Abortion - etiology (6) Immunologic factors l Role is undefined and controversial l 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) More recent findings: l Antiphospholipid syndrome (autoimmune) anticardiolipin antibodies lupus anticoagulants l Activated protein C resistance (genetic) Clinical features : thrombosis, preg. wastage, complications of pregnancy. Management: Prednisone, Aspirin (mini doze), Heparin, Clexane

Recurrent Abortion - etiology (8) Toxic and environmental factors l anesthetic gases ? l alcohol l smoking l environmental pollutants

Recurrent Abortion - etiology (9) Chronic Disease l any chronic disease l maternal congenital cardiac disease l hypothyroidism (rare cause) l diabetes mellitus (advanced dis.) l Systemic Lupus Erythematosus

repeated abortions genetic (5%) anatomy (6-12%) endocrine (15-20%) infections (5%) others: APCR cardiolipin unexplained 50-60%

Preconceptual evaluation of couples with recurrent abortions l 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 management following recurrent abortions l treatments are as yet poorly validated l as many as % of pregnancies are successful even after 3 previous failures Treatment: l general management guidelines (bed rest, coitus)? l general (HCG, progesterone) l specific (surgery, cerclage, progesterone, steroids, minidoze aspirin, clexane, antibiotics)

Differential Diagnosis of suspected early pregnany & vaginal bleeding l early viable & non viable pregnancy l ectopic pregnancy l other causes of enlarged uterus Diagnostic aids: l clinical assessment l sonography l laparoscopy (culdocentesis)

Abortion - Aim of Treatment l Uterine evacuation l avoidance of infection l prevention of Rh sensitization

Evacuation of the uterus - technical aspects “menstrual regulation” l suction curettage l sharp curettage l cervical dilatation: hegar, laminaria, balloon l anesthesia: general, paracervical, sedation l mid trimester abortions: route: intraamniotic or extraamniotic agent: prostaglandins (hypertonic solutions) l antiprogesterone: RU486

Complications of uterine evacuation l Early bleeding, coagulation disorders (IUFD) cervical laceration, perforation l Delayed retained products, infection, bleeding l Late chronic infection infertility, ectopic pregnancy Rh sensitization psychological sequelae

ECTOPIC 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 – Incidence ? in USA – 1992 – 20/1000 reported preg. higher rate in older women & multigravid women increasing due to: increased salpingitis improved diagnostic techniques

ECTOPIC PREGNANCY – mortality l Major cause of maternal death most common cause in first half of preg. l 34 deaths in 1989, USA l 4 deaths per 10,000 women with ectopic (USA, 1989) l Cause: blood loss – 88% infection - 3% anesthesia complications – 2%

ECTOPIC PREGNANCY – etiology l Infection: major cause of 1 st episode; due to morphologic changes l in 40% (1 st episode) cause unknown: physiologic: delay of passage of embryo to uterine cavity more than 7 days – when implantation occurs ovulation from contralateral ovary – uncommon hormonal imbalance (ovulation induction, prog.- releasing IUD)  impaired tubal transport

ECTOPIC PREGNANCY – tubal pathology Salpingitis (6 fold increased risk of TP) l  agglutination of the plicae (folds) of the endosalpinx  sperm passes, but larger morula does not. l Adhesions between tubal serosa and bowel or peritoneum  altered tubal motility l Prior ectopic preg. l Prior tubal surgery

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

ECTOPIC PREGNANCY – pathology Tubal – 98 %, mostly in the ampullary portion Abdominal – 1.4%, mostly secondary Ovarian/cervical - < than 1%

ECTOPIC PREGNANCY – pathology (cont.) l The morula does not grow mainly in the tubal lumen. l The trophoblast invades the muscularis of the oviduct and grows mainly between the lumen of the tube and its peritoneal covering l Hemorrhage is mainly extraluminal l Rupture: the serosa is streched by bleeding, producing necrosis secondary to an inadequate blood supply

ECTOPIC PREGNANCY – pathology, cont. l Slow growth of trophblastic tissue  slow rise of BHCG l Endometrium:secetory – 40% proliferative – 20% decidual – 20% arias stella (endometrial glands hypertrophied, hyperchromatism, pleomorphism, increased mitotic activity) – 20% l Decidual cast: all the decidua passing through the cervix (DD – abortion)

ECTOPIC PREGNANCY – symptoms l Abdominal pain – nearly universal l Amenorrhea l Vaginal bleeding l Dizziness, fainting l Often, atypical presentation

ECTOPIC PREGNANCY – signs l Adnexal tenderness l Abdominal tenderness l Adnexal mass l Uterine enlargement l Orthostatic changes l Fever - uncommon

ECTOPIC PREGNANCY – diagnosis Serial testing l Beta HCG normal preg. – doubling every 2-3 days ectopic preg. - slow rise falling levels l Progesterone (less than 5 ng/ml)

ECTOPIC PREGNANCY – diagnosis (cont.) l Ultrasound normal preg. – at BHCG mIU/ml a gestational sac in seen ectopic preg. – no IU sac presence of adnexal mass or gestational sac in oviduct l D&C l Culdocentesis l Laparoscopy

ECTOPIC PREGNANCY – management l Surgery: mostly laparoscopically salpingectomy, salpingostomy segmental resection l Persistent EP: 5% following salpingostomy l Medical Therapy – methotrexate success: low BHCG - < 5,000 - above 90% > 15,000 – 68% l Expectant management l Remember the Rh factor

ECTOPIC PREGNANCY – subsequent conception l Following ectopic – 60%-70% conceive  1/3 ectopic l Higher conception rates (above 80%) following unruptured EP, conservative treatment, no infection l Repeat EP – following 1 EP – 20 % (8% to 27%) following 2 EP – nearly half