Avoiding the Pitfalls: 1st trimester pregnancy complications Eve Espey, MD, MPH

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Lecture Objectives Understand steps in diagnosis in women with bleeding, cramping and a positive pregnancy test Initiate appropriate management for miscarriage, ectopic and threatened abortion Understand medical and surgical approaches to the management of miscarriage and ectopic pregnancy

The punch line… Don’t nuke a normal pregnancy or miss an ectopic Place an IUD immediately after D&C for miscarriage

The ER calls: “We’ve got a gal here with bleeding, pain and a positive pregnancy test”

Puny differential…. Normal pregnancy Miscarriage Ectopic

Few tools Ultrasound Quantitative hCG Experience Common sense Luck!

But high impact… One of the top reasons OB-GYNs are sued: MTX given to a normal intrauterine pregnancy Ectopic pregnancy still causes maternal mortality Dealing with miscarriage in a sensitive way is paramount to women

Landmarks in Early Pregnancy Uterus outline Sub-chorionic bleed Embryo Yolk sac Gestational sac Choriodecidual reaction Vaginal Ultrasound Ultrasound can be useful in identifying an early intrauterine pregnancy before the procedure and its absence after the procedure. In pregnancies < 5 weeks, the gestational sac may be difficult to find. There will be a thick decidual shadow with an intra- or extra- uterine pregnancy. The features to look for when performing a vaginal ultrasound to determine gestational age for early abortion are: the presence of the gestational sac the presence of an embryonic structure the presence of the yolk sac the presence of cardiac activity.

Transvaginal ultrasound: What you should see, when you should see it 5 weeks ----> Gestational sac (5mm) 6 weeks ----> Yolk sac 7 weeks ----> Cardiac motion Maintain a healthy skepticism about the date of the LMP

Case 17 y/o G2P0 presents with bleeding, cramping, positive pregnancy test Differential Normal pregnancy Miscarriage Ectopic? At every step of the workup, I ask residents to consider what the differential is and has an ectopic been ruled out. Sac = 5 4/7 weeks

Miscarriage vs. normal pregnancy? Quantitative hCG approach: The AVERAGE hCG rise over 48 hours in a normal pregnancy is 124% Day 0 = 1,700 Day 2 = 4,400 Rise = 158% Likely diagnosis?

What if the quants had been..? Day 0 = 1,700 Day 2 = 2,200 Rise = 29% Likely diagnosis? The MINIMUM hCG rise over 48 hours in a normal pregnancy is 53%

1st Trimester hCG J Clin Endocrinol Metab 1979;49:917

Caveats 15% of women with IUP have an “abnormal” rise in hCG in the first 40 days 17% of ectopic pregnancies have a normal rise in hCGs over 48 hours at least once in early pregnancy Kadar et al.Obstet Gynecol 1981;58:162

Case 32 y/o G2P1 at 7 weeks from LMP Presents with bleeding, cramping, positive pregnancy test hCG = 5,277

Discriminatory zone Transvaginal U/S Transabdominal U/S Beta HCG = 1500 - 2000 mIu/ml Transabdominal U/S Beta HCG = 3,600 mIu/ml If HCG > discriminatory zone and no gestational sac seen, consider ectopic pregnancy till proven otherwise

Day 8 hCG = 580 Ultrasound:

Oops! Ectopic pregnancy

ECTOPIC PREGNANCY Most common cause of maternal death in early pregnancy 20 deaths per year in the US 1970 17,800 cases Fatality 35/10,000 1992 108,800 cases Fatality 3.4/10,000 Risk factors: Prior tubal sterilization 10% Hx Salpingitis.....4X Linear salpingostomy.....10X Ovulation induction.....4X Most cases have no known risk factor! Minority race

Ectopic: Management options Laparoscopy Salpingostomy 5-20% persistent ectopic Monitor with hCG to 0 Treat with MTX Salpingectomy Laparotomy Medical management Expectant management

Medical management of ectopic pregnancy using Methotrexate: Single, two or multi-dose regimens Reported success: 71%-94% Patient selection Stable No IUP on ultrasound or villi on D&C Labs normal: AST, WBC, platelets, creatinine Relative contraindications hCG > 5,000 Cardiac activity in the tube Sac > 3.5 cm

Single dose MTX Day 0: hCG, CBC, Platelets, Rh, AST, Cr Day 0: MTX 50mg/m2 IM Day 4: Quantitative hCG Day 7: Quantitative hCG If HCG does not decrease by at least 15% from Day 4, repeat MTX Weekly hCG until < 5

Failure…. If pretreatment Bhcg >5000 failure rate is around 14% Consider two-dose regimen if Bhcg >5000

Fertility following treatment for ectopic pregnancy Author Tx IUP Repeat ectopic Sherman 1982 Salpingectomy 72% 6% Sherman 1982 Salpingostomy 83% 6% Stovall 1993 Medical 70% 9%

Miscarriage

Spontaneous abortion About 25% of women experience a miscarriage. Approximately 15% of clinically recognized pregnancies spontaneously abort in the first or early second trimester. Up to 33% of all pregnancies end in miscarriage.

Management options for miscarriage Expectant management Misoprostol D&C Suction MVA

Misoprostol for miscarriage Pooled outcomes Treatemtent Success rates Placebo 16-60% Single dose misoprostol 25-88% Repeat dose x 1 if incomplete at 24 hours 80-88% Success rate depends on type of miscarriage -100% with incomplete abortion - 87% for all others Wood SL, Obstet Gynecol 2002; Bagratee JS, Hum Reproduct 2004; Blohm F, BJOG: Int J Obstet Gynecol 2005

Misoprostol for miscarriage: Note – off label use! Gestational sac or CRL up to 10 weeks No embryo or no fetal cardiac activity Rh, hematocrit 800 mcg misoprostol x 2 doses Intravaginal home administration x 1 dose Repeat after 24 hours if no tissue Ibuprofen + Tylenol with codeine If no passage within a week, RTC for options

Suction curettage

Manual Vacuum Aspirator (MVA)

Anesthesia options “Vocal local” Oral analgesia + paracervical block Ibuprofen 800 mg Percocet and 1 mg lorazepam IV sedation + paracervical block + Fentanyl 50-100 mcg Midazolam 1-2 mg Regional anesthesia (spinal) General anesthesia or deep sedation CORE SLIDE

A hair-raising tale: 31 y/o G3P2 presents to ER with “severe LLQ pain” and positive pregnancy test Benign pelvic exam, + hCG Ultrasound: “No IUP, left adnexal mass with surrounding echogenic fluid and free fluid in pelvis concerning for ruptured ectopic” hCG = 1,003

Day 0 Ectopic pregnancy vs. early IUP Offered methotrexate Patient declined: desired pregnancy Plan: Repeat hCG in 48 hours

Day 1 assessment Continued pain, back to emergency room HR 93, BP 148/71, bilateral adnexal tenderness and rebound Ultrasound: “Small hypoechoic focus in uterus, possible pseudosac. Left adnexal mass with interval development of heterogeneous material/free fluid” hCG: 1,419 (55% rise)

Day #1 management Laparoscopy 400 cc hemoperitoneum, “no active bleeding site determined” Attempted salpingostomy followed by left salpingectomy Discharged on POD #1

Day #7 Pathology sent on Day #1 Checked on Day #7 Pathology Gross: Sectioning through this area demonstrates “presumed villi” Microscopic diagnosis: “No chorionic tissue, no evidence of intratubal gestation

Day 7 Patient called: “final pathology negative for POCs” hCG: 9,417 Triage ultrasound: “Gestational sac measuring 6 weeks, minimal free fluid, right ovary 2.9 cm, circumferential flow, hypoechoic cystic structure within ovary measuring 2 cm, no embryonic pole, no embryonic fetal heart motion.”

Day #7: Management Diagnosis: Presumed ongoing ectopic Radiology ultrasound was ordered but not available since it was the weekend. Given a concerning picture for ectopic, methotrexate was recommended IM MTX 50 mg/m2 Day #11 hCG = 15,168 – not checked, F/U day #14 (7 days after MTX given)

Follow-up Day #14 Day #18 Day #25 Day #30 Ultrasound: 6 ½ week IUP with positive fetal heart motion in the 120s Patient counseled re MTX in setting of normal IUP Day #18 Ultrasound: CRL consistent with 6 ½ weeks with FHM ranging from 0-100 bpm Day #25 Ultrasound: CRL consistent with 6 ½ weeks with no FHM Requests misoprostol for management Day #30 Empty uterus, Paragard IUD placed

Multiple problems “Offered” MTX (instead of dx LSC) on Day 0 with a desired pregnancy Laparoscopy: No active bleeding? Checked pathology on Day 7 Incorrect interpretation of hCG of 9,417 with no fetal heart motion MTX given based on an inadequate U/S Day #11 hCG not checked till Day #14

The devil is in the details hCG and pathology follow-up Beta book system Continuity of physician teams seeing the patient Context—patient course, hCGs and U/S

Classic missed opportunity Ovulation may occur within 10 days Don’t forget contraception Half of pregnancies are unintended May wish to delay another pregnancy even if intended

IUD insertion after 1st trimester uterine aspiration > 700 women undergoing D&C (abortion and miscarriage) from 5-12 weeks Randomized to immediate vs. delayed IUD insertion No significant difference in expulsion risk: 4.5% immediate 2.7% delayed No increase in other complications Bednarek, NEJM 2011

Summary Be meticulous in follow-up of first trimester complications Consider misoprostol and MVA for treatment Don’t forget the IUD!