Obstetric Outcomes and Placental Pathology in Vanishing Twins Conceived via IVF

(1)

Harris AL, Sacha CR, Basnet KK, James EK, Freret TS, Kaimal AJ, et al. Vanishing twins conceived through fresh in vitro fertilization: obstetric outcomes and placental pathology. Obstet Gynecol 2020;135.

The authors provided this information as a supplement to their article.

Appendix 1. Maternal Demographic and Cycle Characteristics at Time of First Oocyte Retrieval Patients (n=860)

Age 34.9 (4.0)

Race

White 669 (77.8%)

Black 33 (3.9%)

Asian 109 (12.4%)

Other 49 (5.7%)

Ethnicity

Hispanic 10 (1.2%)

Non-Hispanic 656 (76.3%)

Other 35 (4.1%)

Not specified 155 (18.5%)

BMI (median, IQR) 23.6 (21.5, 26.9)

Nulliparous 681 (79.2%)

Day 3 FSH 7.1 (2.2)

AMH (2014-2017) 4.0 (4.2)

Infertility Diagnosis

Male factor 391 (45.5%)

Female factor 434 (50.5%)

Tubal factor 130 (15.1%) Ovulatory dysfunction 53 (6.2%)

PCOS 91 (10.6%)

Decreased ovarian reserve 113 (13.1%) Uterine factor 27 (3.1%) Endometriosis 50 (5.8%)

Idiopathic 213 (24.8%)

Other/Non-infertility 32 (3.7%)

(2)

Appendix 2. Pathology Categorization

Pathology Explanation

Anatomic

Small placenta by weight Less than the 10^th percentile by weight for gestational age using standard weight table^a Large placenta by weight Greater than the 90^th percentile by weight for gestational age using

standard weight table^a Marginal cord insertion Umbilical cord inserts less than or equal to 1 cm from the placental margin Membranous cord insertion Umbilical cord inserts into the membranes^b Coiling anomalies Hyper- or hypo coiled umbilical cords (4 or more- or 1 or less- coils in 10 cm on average) or rightward coiled umbilical cord^c

Two vessel cord Single umbilical artery

Membranous vessels Chorionic vessels within the membranes not supported by placental parenchyma Other cord findings e.g. true knots, thin cords, surface nodules, discoloration.

Circummarginate or

circumvallate membranes Abnormal insertion of the membranes central to the margin of the placenta Accessory placental lobe Succinturiate lobe of the placenta separate from the main disk Infectious

ACHA-MIR, grade and/or

stage ≥ 2 Acute chorioamnionitis with moderate to severe maternal inflammatory response ACHA-FIR, grade and/or

stage ≥ 2 Acute chorioamnionitis with moderate to severe fetal inflammatory response^b,d Inflammatory

Villitis of unknown etiology

(VUE), low grade Lymphohistiocytic infiltrate within villi, less than 10 contiguous villi affected in any focus, more than 1 focus needed^b Villitis of unknown etiology

(VUE), high grade Lymphohistiocytic infiltrate within villi with 10 or more contiguous villi involved, more than one focus and more than one slide involved^b

(3)

Chronic deciduitis 50 or more lymphocytes and/or 5 or more plasma cells per high power field in the decidua^e Chronic histiocytic

intervillositis A diffuse infiltrate of histiocytes in the maternal vascular space^f,g Non-specific inflammation

Vascular

Maternal vascular

malperfusion (MVM) Placenta involves two or more of the following: distal villous hypoplasia or accelerated villous maturation, placental infarct, decidual arteriopathy, evidence of acute or chronic abruption, or increased fibrin deposition^b Fetal vascular malperfusion

(FVM), low grade Single focus of less than 45 total avascular villi or villous stromal- vascular karyorrhexis or one large vascular thrombus^b. Fetal vascular malperfusion

(FVM), high grade Greater than one focus, more than 45 total avascular villi or villous- stromal vascular karyorrhexis, more than 1 large vascular thrombi^b. Intervillous thrombi (IVT) Laminated thrombus in maternal vascular space.

Subchorionic thrombi Laminated thrombus in the subchorionic space in the disk.

Septal thrombi Thrombus in the septum or within a septal cyst

Disruption Torn, fragmented, or incomplete disk.

aPinar H, Sung CJ, Oyer CE, Singer DB. Reference values for singleton and twin placental weights. Pediatr Pathol Lab Med. 1996;16(6):901-907.

bKhong TY, Mooney EE, Ariel I, et al. Sampling and definitions of placental lesions: Amsterdam placental workshop group consensus statement. Arch Pathol Lab Med. 2016;140(7):698-713.

cvan Dijk CC, Franx A, de Laat MW, Bruinse HW, Visser GH, Nikkels PG. The umbilical coiling index in normal pregnancy. J Matern Fetal Neonatal Med. 2002;11(4):280-283.

dRedline RW, Faye-Petersen OM, Heller DS, et al. Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol. 2003;6(5):435-448.

eMaroun LL, Mathiesen L, Hedegaard M, Knudsen LE, Larsen LG. Pathologic evaluation of normal and perfused term placental tissue. Pediatr Dev Pathol. 2014;17(5):330-338.

fBoyd TK, Redline RW. Chronic histiocytic intervillositis: a placental lesion associated with recurrent reproductive loss. Human pathology. 2000;31(11):1389-1396.

gChen A, Roberts DJ. Placental pathologic lesions with a significant recurrence risk - what not to miss! APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 2018;126(7):589-601.

Reprinted from Sacha CR, Harris AL, James K, Basnet K, Freret TS, Yeh J, et al. Placental pathology in live births conceived with in vitro fertilization after fresh and frozen embryo transfer. Am J Obstet Gynecol. 2019 Oct 4. pii: S0002-9378(19)31213-X. Copyright 2019, with permission from Elsevier.

(4)

Appendix 3. Subgroup Analysis of Empty Gestational Sac, Vanishing Twin Pregnancies vs. Singleton Pregnancies Empty

Gestational Sac (n=11)

Vanishing twin <8w

(n=51) Vanishing twin >8w (n=20) P-value Placental pathology

Any anatomic

pathology 4 (36%) 38 (75%) 15 (75%) 0.51

Small (<10%ile) 1 (9%) 27 (53%) 12 (60%) 0.44

Large (>90%ile) 1 (9%) 5 (10%) 0 (0%) 0.12

Marginal cord insertion 1 (9%) 3 (6%) 2 (10%) 0.81

Membranous cord

insertion 2 (18%) 7 (14%) 3 (15%) 0.93

Membranous vessels 1 (9%) 2 (4%) 0 (0%) 0.43

All other cord findings 1 (9%) 0 (0%) 1 (5%) 0.14

Circummarginate or circumvallate membranes

2 (18%)

4 (8%) 0 (0%) 0.17

Accessory placental lobe 2 (18%) 7 (14%) 2 (10%) 0.81

Any infectious

pathology 2 (18%) 14 (27%) 7 (35%) 0.57

Acute chorioamnionitis with maternal inflammatory response, Moderate to Severe

2 (18%)

5 (10%) 2 (10%) 0.05

Acute chorioamnionitis with fetal inflammatory response, Moderate to Severe

0 (0%)

3 (6%) 1 (5%) 0.88

Any inflammatory

pathology 2 (18%) 8 (16%) 3 (15%) 0.53

(5)

Data are mean+ SD, n (%), or median (interquartile range).

Villitis of unknown

etiology, low-grade 1 (9%) 2 (4%) 1 (5%) 0.77

Villitis of unknown

etiology, high-grade 0 (0%) 1 (2%) 2 (10%) 0.21

Chronic deciduitis 1 (9%) 3 (6%) 1 (5%) 0.90

Chronic Histiocytic

Intervillositis 0 (0%) 0 (0%) 0 (0%) 0.29

Any vascular pathology 3 (27%) 34 (67%) 13 (65%) 0.93

MVM 0 (0%) 21 (41%) 7 (35%) 0.25

FVM low grade 1 (9%) 5 (10%) 1 (5%) 0.81

FVM high grade 0 (0%) 0 (0%) 0 (0%) --

Intervillous thrombi 9 (18%) 4 (20%)

Subchorionic thrombi 1 (2%) 0 (0%)

Septal thrombi 0 (0%) 0 (0%)

Placental disruption 7 (14%) 4 (20%)