08.31.23 CM_Abnormal First Trimester Pregnancies_Cullen_Notes (2).pdf

August 31, 2023 Abnormal First Trimester Pregnancies Page 1 of 9 Abnormal First Trimester Pregnancies Instructor: Danielle Cullen, MD ([email protected]) Block 5: Urology/Endocrine/Reproduction Thread: Clinical Medicine Conflicts of Interest: Dr. Cullen has no conflicts of interest to...

August 31, 2023 Abnormal First Trimester Pregnancies Page 1 of 9 Abnormal First Trimester Pregnancies Instructor: Danielle Cullen, MD ([email protected]) Block 5: Urology/Endocrine/Reproduction Thread: Clinical Medicine Conflicts of Interest: Dr. Cullen has no conflicts of interest to disclose. Learning Objectives By exam time, you should be able to do the following: • Define spontaneous abortion (SAB), ectopic pregnancy, and molar pregnancy • Explain risk factors and etiologies of SAB, ectopic, and molar pregnancies • Recognize clinical presentations and diagnosis of SAB, ectopic, and molar pregnancies • Describe management options for SAB, ectopic, and molar pregnancies • Recognize the impact of recent legislation on abnormal 1st trimester pregnancy management Study Questions 1. A 38-year-old G3P2012 patient presents to the emergency room with abdominal cramping and vaginal bleeding. Last menstrual period is reported to be about 8 weeks ago. She lives with her two children and husband and does not smoke or drink alcohol. Vitals are as follows: HR 70 BP 120/75 T 98 On exam, her uterus is small, mildly tender, with a closed cervical os. There is slow dark brown bleeding from the cervix. An ultrasound shows a 7 week size fetus (10mm in length) inside the uterus without a heartbeat. There are no adnexal masses or free fluid in the pelvis. Labs: WBC 8.2 Hemoglobin 11.5 Hct35 Platelets 250  What is the diagnosis?  What risk factors does she have and what is the likely etiology?  What other labs should be ordered?  What are management options for this patient? August 31, 2023 2. Abnormal First Trimester Pregnancies Page 2 of 9 A 24 year old G1P0 patient presents to the office with pelvic cramping. She missed her menstrual cycle last week. On exam she has mild uterine and adnexal tenderness and no vaginal bleeding. Cervical os appears closed. Her urine pregnancy test is positive and a bHCG confirm pregnancy at 700 IU. A pelvic ultrasound shows no intrauterine pregnancy and a 2 cm adnexal mass. PMH is significant for ruptured appendicitis at age 13yo. She smokes ½ PPD.  What is the differential diagnosis for this patient?  What are her risk factors?  What are the next steps in evaluation? Spontaneous Abortion (SAB) Definition: Loss of a pregnancy up to 20 gestational weeks Incidence 8 to 20 percent Approximately 80% of pregnancy loss happens in the 1st trimester Risk Factors A. Age of the pregnant person (or rather the ovum) a. Age 20-30y: 9-17% b. Age 35y: 20% c. Age 40y: 40% d. Age 45y: 80% B. Previous spontaneous abortion a. 20% risk after one SAB b. 28% after two SABs c. 43% after 3+ consecutive SABs d. Recurrent SAB is defined as 2+ miscarriages in a rowi. etiology is undetermined in 50% of patients with recurrent SAB ii. occurs in about 2-3% of couples iii. may be due to “recurring risk factors” or may just be bad luck iv. recurring risk factors include: 1. Thrombotic disorders (APLS 2. Parental genetic difference (balanced translocation, inversions…) August 31, 2023 Abnormal First Trimester Pregnancies Page 3 of 9 3. Endocrine disorders: thyroid autoimmunity, DM, PCOS 4. Uterine malformations (septum, submucous fibroids) C. Smoking: heavy smoking associated with increased risk of SAB D. Alcohol: moderate to high consumption E. Cocaine use Etiology of SAB A. Chromosomal abnormalities: this is the cause in >50% of pregnancy loss a. Most common chromosomal causes of SAB are T16, 45XO, T22 and T21 B. Uterine abnormalities: uterine septum, submucous or intracavitary myomas, endometrial polyps C. Infections: TORCH infections, STIs, endometritis, chorioamnionitis. D. Endocrinopathy: thyroid disorders and pregestational diabetes E. Hypercoagulable state F. Unexplained Clinical Presentation Vaginal bleeding — common in the first trimester, occurring in 20 to 40 percent of pregnant women. Pelvic pain/cramping Often asymptomatic, found incidentally on ultrasound Miscarriage Type Characteristics Cervix Ultrasound Complete Bleeding, all tissue passed Closed Empty uterus Incomplete Bleeding, some tissue passed Dilated Retained tissue Threatened Bleeding Closed Viable pregnancy Missed Asymptomatic or light bleeding Closed Non-viable pregnancy Inevitable (cervical incompetence) Bleeding +/- pain Dilated Viable pregnancy Septic Intrauterine infection Closed or dilated, purulent discharge Retained tissue August 31, 2023 Abnormal First Trimester Pregnancies Diagnostic Evaluation A. History: pain, bleeding, menstrual history B. Pelvic examination 1. Cervical dilation 2. Products of conception 3. Uterine size 4. Uterine tenderness or purulent discharge C. Pelvic ultrasound 1. Gestational sac - During embryologic development, the gestational sac develops, followed by the yolk sac, and then the embryo 2. Yolk sac - Absence of a yolk sac in a gestational sac >8 mm indicates abnormal pregnancy 3. Embryo - Absence of embryo in a gestational sac >25 mm indicates abnormal pregnancy 4. Fetal cardiac activity confirms live pregnancy, but a low heart rate is associated with increased risk of SAB D. Laboratory evaluation 1. Human chorionic gonadotropin — Greater than 35 percent decline in serum hCG based upon two measurements at least two days apart suggest a SAB 2. Blood type and antibody screen — Women with bleeding in pregnancy who are Rh(D)-negative should be given anti-D immune globulin 3. Complete Blood Count (CBC) --- should be aware of starting hemoglobin Management Choice of management depends on medical necessity and largely patient preference A. Expectant management a. Recommended only in 1st trimester b. 80% of people will expulse all products within 8 weeks c. Heavy bleeding and cramping at home Page 4 of 9 August 31, 2023 Abnormal First Trimester Pregnancies Page 5 of 9 B. Medication (Misoprostol OR mifepristone + misoprostol) a. Only if no infection, hemorrhage, severe anemia, or bleeding disorders b. Typically limited to 1st trimester, unless done inpatient c. Can shorten the time to complete expulsion for those who prefer to avoid operative management d. Mifepristone (progesterone antagonist) followed in 24 hours by misoprostol (prostaglandin) is most effective- 80-85% within 7 days e. Can also use misoprostol alone- mifepristone is highly regulated C. Surgery (Dilation and curettage or Manual Uterine Aspiration) a. Urgent for those with hemorrhage, hemodynamic instability, or signs of infection b. Preferred in patients with significant anemia, bleeding d/o and cardiovascular disease c. Patients may prefer this option for immediate completion of the process with less follow-up Ectopic Pregnancy Definition: Embryo implanted outside of the uterine cavity • Pregnancy of unknown location (PUL): Has not met criteria for definitive intrauterine pregnancy (IUP) or ectopic Incidence: about 2% of all pregnancies; 18% of pregnancies who present with pain and bleeding (thus, we follow these patients closely) Anatomic Locations A. Fallopian tube >90% B. Abdomen ~1% C. Cervix ~1% D. Ovary ~1-3% E. Cesarean scar ~1-3% August 31, 2023 Abnormal First Trimester Pregnancies Page 6 of 9 Risk Factors : Tubal scarring and ciliary dysfunction A. B. C. D. E. F. G. Half of people with ectopics have no risk factors Previous ectopic pregnancy: 10% recurrence after 1 ectopic, 25% risk after 2+ Pelvic infections (PID, ruptured appendicitis) History of tubal surgery or pelvic surgery Endometriosis (scar tissue) IVF and infertility Smoking (ciliary dysfunction) Clinical Presentation A. Pelvic pain and bleeding with positive HCG B. Sometimes sudden severe pain in setting of rupture C. Unstable vital signs or dropping hemoglobin Diagnosis A. History and risk factors B. Exam - Assess for hemodynamic instability C. Pelvic ultrasound a) Definitive: TVUS identifying gest sac with yolk sac or embryo outside of the endometrial cavity b) Suspicious: a. Mass or mass with hypoechoic area separate from the ovary b. HCG above discriminatory level (3500) with no gestational sac c. Free fluid (blood) in the pelvis c) Ruled out: Definitive IUP (except in rare heterotopic cases) Treatment A. Medical (Methotrexate) a. Folate antagonist: Binds to dihydrofolate reductase site  interrupts synthesis of purine nucleotide and the amino acids serine and methionine  inhibition of DNA synthesis/repair and cell replication b. Affects all actively proliferating tissues (bone marrow, buccal mucosa, intestinal mucosa, respiratory epithelium, malignant cells, trophoblastic tissue) c. Directly toxic to hepatocytes and cleared renally, so liver and kidney disease are exclusions August 31, 2023 Abnormal First Trimester Pregnancies Page 7 of 9 B. Surgical removal of pregnancy (salpingotomy) or entire fallopian tube including pregnancy (salpingectomy) Molar Pregnancy Definition: Abnormal chorionic villi with trophoblast hyperplasia leading to hydropic placental villi, related to overexpression of paternal genes. It is considered premalignant and can undergo malignant transformation to GTN (gestational trophoblastic neoplasia) Incidence: Widely different geographically, 1:1000 in North America and Europe A. Complete mole (Diploid) a. “Snowstorm”/”cluster of grapes” pattern on ultrasound b. ~80% homozygous 46XX, single sperm genome duplication after fertilization of an ovum that lost its DNA during meiosis c. ~20% due to dispermic fertilization of ovum lacking DNA (can be 46XX or 46XY) d. Gestational Trophoblastic Neoplasia (GTN) develops in ~20% August 31, 2023 Abnormal First Trimester Pregnancies Page 8 of 9 B. Partial mole (Triploid) a. Fetus with abnormal placenta on ultrasound b. Usually fertilization of a haploid ovum by two sperm (can be 69XXX, 69XXY, or 69XYY) c. Presence of fetus, may have cardiac activity, often misdiagnosed as SAB and diagnosis made only on pathology d. hCG levels elevated but lower than in complete mole e. GTN develops in ~4% of these patients C. Risk factors a. Extremes of reproductive age: <15yo or >45y i. 5-10x greater risk for those >45yo b. History of molar pregnancy D. Clinical Presentation and Diagnosis a. Vaginal bleeding is most common symptom b. Hyperthyroidism/thyroid storm, hyperemesis, early onset preeclampsia c. Uterus size larger than expected for gestational age, especially with complete mole d. Significantly elevated HCG level (>100,000) suggestive e. Pelvic ultrasound with classic cystic spaces in placenta; theca lutein cysts are also highly suspicious f. Pathologic evaluation of tisue after uterine evacuation E. Management a. Preferred: Suction D&C (surgical evacuation of the uterus) b. Hysterectomy is alternative to those who have completed child bearing (80% risk reduction in GTN) c. Post-op monitoring for post-molar GTN d. Serial HCG monitoring weekly until zero and then monthly (3 months after complete and 1 month after partial) e. Reliable contraception until completion of post-molar surveillance August 31, 2023 Abnormal First Trimester Pregnancies Page 9 of 9 Answers to Study Questions These answers are not meant to be all encompassing; rather they are examples of the types of thought processes needed for application of the material. 1. A 38-year-old G3P2012 patient presents to the emergency room with abdominal cramping and vaginal bleeding. Last menstrual period is reported to be about 8 weeks ago. She lives with her two children and husband and does not smoke or drink alcohol. Vitals are as follows: HR 70 BP 120/75 T 98 On exam, her uterus is small, mildly tender, with a closed cervical os. There is slow dark brown bleeding from the cervix. An ultrasound shows a 7 week size fetus (10mm in length) inside the uterus without a heartbeat. There are no adnexal masses or free fluid in the pelvis. Labs: WBC 8.2 Hemoglobin 11.5 Hct35 Platelets 250 2.  What is the diagnosis? Missed abortion. The fetus is measuring large enough that absence of a heartbeat is diagnostic for pregnancy loss.  What risk factors does she have and what is the likely etiology? Age >35yo  What other labs should be ordered? Type and Screen  What are management options for this patient? Expectant management, medical management and surgical evacuation A 24 year old G1P0 patient presents to the office with pelvic cramping. She missed her menstrual cycle last week. On exam she has mild uterine and adnexal tenderness and no vaginal bleeding. Cervical os appears closed. Her urine pregnancy test is positive and a bHCG confirm pregnancy at 700 IU. A pelvic ultrasound shows no intrauterine pregnancy and a 2 cm adnexal mass. PMH is significant for ruptured appendicitis at age 13yo. She smokes ½ PPD.  What is the differential diagnosis for this patient? Ectopic pregnancy versus early intrauterine pregnancy with ovarian/adnexal mass. Given that the HCG level is below the discriminatory zone, this is technically a pregnancy of unknown location, but is suspicious for ectopic given the adnexal mass.  What are her risk factors? History of pelvic infection and smoking  What are the next steps in evaluation? Repeat HCG level in 48 hours; given the patient strict precautions for signs/symptoms of ruptured ectopic