Richard Scott Lucidi
History of present illness
A 24-year-old gravida 3, para 0 woman presents to your acute care clinic with complaints of vaginal bleeding that she describes as“like a period.”She is currently at 8 weeks’gesta- tional age confirmed by an ultrasound 2 weeks ago that showed a 5 mm fetal pole with cardiac motion. She denies any pain but has symptoms consistent with early pregnancy including breast tenderness and nausea. She is tearful and worried about this pregnancy since she has had two prior pregnancy losses. The first pregnancy passed spontaneously without complications. Her second pregnancy was managed with cervical dilation and uterine curettage; however, the surgical pathology showed no products of conception and a second curettage was successfully performed with products of conception obtained. Her only medication is prenatal vita- mins. A prior three-dimensional pelvic ultrasound showed a septate uterus (Fig. 64.1.)
Physical examination
General appearance: Well-developed, well-nourished woman in no discomfort but with mild emotional distress
Vital signs:
Temperature: 37.0°C Pulse: 90 beats/min
Blood pressure: 102/62 mmHg Respiratory rate: 16 breaths/min Oxygen saturation: 99% on room air BMI: 23 kg/m2
Pelvic: Blood is on the perineum and in the
vagina. Moderate active bleeding is present from the cervical os. The uterus is anteverted, six weeks’size, and nontender. No cervical motion tenderness is present.
The cervix is closed. There is no adnexal mass or tenderness
Laboratory studies:
hCG: 9200 mIU/mL (normal<5 mIU/mL) Hb: 14.3 g/dL (normal 12–15 g/dL) Ht: 43% (normal 34.8–45%)
Imaging: A pelvic ultrasound is obtained that shows an intrauterine pregnancy with an irregularly shaped gestational sac and a 5-mm fetal pole without cardiac motion
How would you manage this patient?
This patient is hemodynamically stable; however, the lack of interval growth between the ultrasound exams two weeks apart and the absence of previously seen cardiac motion confirms the diagnosis of a missed abortion. Since this is her third miscarriage, the diagnosis of recurrent pregnancy loss (RPL) is also appropriate.
Expectant management, medical management, and surgical management with dilation and curettage are options for the management of a missed abortion in a stable patient. Since she also has the diagnosis of recurrent pregnancy loss, con- sideration should be given to performing a dilation and curettage in order to obtain tissue for cytogenetic analysis [1]. Karyotype analysis of the products of conception would provide information to assess whether the loss was random or likely due to her structural uterine abnormality. An abnormal karyotype in the products of conception may guide further evaluation toward parental chromosomal abnormalities.
A normal karyotype in the products of conception may guide the evaluation toward endocrine abnormalities, anti- phospholipid antibodies, or toward the treatment of her uterine septum.
Ultrasound guidance during the dilation and curettage procedure would help to assure that the products of concep- tion are evacuated. With a uterine septum, it is possible to curette the uterine cavity on only one side of the septum and failing to obtain tissue on the opposite side of the septum. This scenario happened in the patient’s second miscarriage.
Patients with a septate uterus have a high incidence of first-trimester loss (44%) and surgical correction of the septum decreases the incidence (17%) [2,3]. This patient should be scheduled for hysteroscopic correction of her septum in a nonemergent setting following resolution of this pregnancy.
Although a probable cause of her RPL is evident with the septum, further evaluation of other causes including hormonal abnormalities (thyroid dysfunction, uncontrolled diabetes, hyperprolactinemia), antiphospholipid antibodies (lupus anti- coagulant, anti-cardiolipin antibodies, anti-β2 glycoprotein antibodies) and balanced chromosomal abnormalities (trans- locations, inversions) should be offered as more than one etiologic factor is often present [4].
Pregnancy loss is an emotional experience and couples with RPL may have heightened grief, depression, or anxiety. Sensi- tivity to these issues is necessary and psychological counseling should be offered.
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
Recurrent pregnancy loss
Recurrent pregnancy loss (RPL) is defined as two or more consecutivefirst-trimester losses of clinical pregnancies [2,3].
Although 15–25% of pregnancies result in a spontaneous loss, only 5% of women will have two consecutive losses, and only 1% will have three or more losses. The risk of miscarriage in subsequent pregnancies is also influenced by the number of prior losses. After 2 losses the risk is 30% and after 3 losses the risk is 33% [3]. Thus, the definition of RPL is based on both decreased prevalence and increased risk.
The definition also specifies losses of clinical pregnancies.
Clinical pregnancies are defined by ultrasonic visualization or
histopathologic examination [1]. Ectopic pregnancies result from a different set of possible etiologies and are not included.
Also, positive pregnancy tests that resolve spontaneously – chemical pregnancies–are not included since there is no data on associated risks following these pregnancies.
Although the potential etiologies of RPL are controversial, consensus exists for a small number of accepted etiologies (Table 64.1) including uterine structural abnormalities, paren- tal chromosomal abnormalities, maternal endocrine disorders, and antiphospholipid antibody syndrome (APS).
Women with congenital uterine malformations have a higher incidence of pregnancy loss. Although no prospective
Table 64.1 Etiologies of recurrent pregnancy loss
Etiology Recommended tests Treatment
Anatomic Sonohysterogram or
Hysterosalpingogram or Hysteroscopy
Hysteroscopic removal of uterine septum, synechia or submucous myomas
IVF with gestational surrogate for uncorrectable abnormalities Parental chromosomal
abnormalities Karyotype Preimplantation genetic diagnosis
Donor sperm or donor oocytes Endocrine Thyroid-stimulating hormone
Prolactin
Fasting blood sugar or HgbA1C if symptomatic
Thyroid replacement Bromocriptine
Insulin or insulin-sensitizing agents
Antiphospholipid
antibody syndrome Lupus anticoagulant Anticardiolipin IgG and IgM Anti-β2 glycoprotein IgG and IgM
Aspirin 81 mg
Heparin 5000 U SQ BID with pregnancy
BID, twice a day; HgbA1C, hemoglobin A1C; IgG, immunoglobulin G; IgM, immunoglobulin M; IVF, in-vitro fertilization; SQ, subcutaneous.
Í
Fig. 64.1 Three-dimensional pelvic ultrasound.
trials exist on which to base firm conclusions, the general consensus is that women with RPL be evaluated with hyster- osalpingogram, sonohysterogram, or hysteroscopy and that identified abnormalities can be more fully evaluated by MRI or three-dimensional ultrasound. Consensus also exists that those women with a significant uterine abnormality undergo surgical correction [2]. This patient has a clearly visible septum on three-dimensional ultrasound and hysteroscopic resection should be offered.
Balanced structural chromosome abnormalities are present in 2–5% of couples with RPL. Balanced translocations, either reciprocal or Robertsonian, are the most common type of structural abnormality in patients with RPL. When germ cells with these balanced translocations undergo meiosis they result in unbalanced oocytes or sperm with high frequency. These abnormalities are thought to be more commonly inherited from the mother since unbalanced sperm are less likely to result in fertilization; however, karyotype testing of both part- ners is indicated. Couples found to have a chromosomal abnormality should be referred for genetic counseling. Treat- ment options include donor eggs or sperm, and preimplanta- tion genetic diagnosis (PGD) of embryos created via in-vitro fertilization.
The American Society of Reproductive Medicine (ASRM) recommends screening patients with RPL for thyroid and prolactin abnormalities with TSH and prolactin levels [2].
Poorly controlled diabetes is also a risk factor for miscarriage
and women with symptoms of diabetes should be screened with a fasting blood glucose or HbA1C.
Antiphospholipid antibody syndrome (APS) is associated with RPL and treatment with aspirin and heparin improves pregnancy outcomes. Patients with RPL should be screened for the lupus anticoagulant, anticardiolipin immunoglobulin G and immunoglobulin M (IgG and IgM), and anti-β2 glyco- protein IgG and IgM. Positive tests should be confirmed 12 or more weeks after the initial test, and patients with persistent titers should be treated with aspirin 81 mg daily and 5000 U of unfractionated heparin SQ BID.
For more than 50% of couples with RPL, no etiology will be identified following evaluation. However, live birth rates of 35–85%, depending on age and parity, are typically achieved in the subsequent pregnancy without treatment.
Key teaching points
Recurrent pregnancy loss (RPL) is defined as two or more consecutive losses of clinical pregnancies.
Structural uterine abnormalities, parental chromosome abnormalities, maternal endocrine abnormalities, and antiphospholipid antibodies are potential causes of RPL.
No cause is identified in more than 50% of couples with RPL.
The prognosis in subsequent pregnancies for live-birth is good.
References
1. Royal College of Obstetricians and Gynaecologists.The Investigation And Treatment Of Couples With Recurrent First-Trimester And Second Trimester Miscarriage. Green-top Guideline 17, April 2011. Available athttp://www.
rcog.org.uk/files/rcog-corp/
GTG17recurrentmiscarriage.pdf.
2. Practice Committee of the American Society for Reproductive Medicine.
Evaluation and treatment of recurrent pregnancy loss: a committee opinion.
Fertil Steril2012;98:1103–11.
3. American College of Obstetricians and Gynecologists. Management of recurrent pregnancy loss. Practice Bulletin No. 24.
Int J Gynecol Obstet2002;78:179–90.
4. Petrozza JC.Recurrent Early Pregnancy Loss. Available athttp://emedicine.
medscape.com/article/260495-overview.
Case 64: A 24-year-old woman with her third pregnancy loss