Evidence Table 10. KQ 3 Reproductive outcomes

Study DescriptionStudy Design, Interventions, and Patient PopulationInclusion/ Exclusion Criteria and Other DetailsFibroids CharacteristicsOutcomesNotes/Quality Rating
Author:Design:Inclusion criteria:Baseline uterine size:Cumulative pregnancy rate, N (%):Quality:
Bulletti et al., 2004Prospective cohort
  • Nulliparity
  • Age 25 to 39
  • ≥1 fibroid > 5 cm with tubal occlusion
NRG1: 28 (33)Overall quality score: poor
Country and setting:Intervention:Exclusion criteria:Number of fibroids:G2: 13 (15)INTERNAL VALIDITY: poor
Italy, Academic medical centerMyomectomy before IVF
  • Male factor infertility
  • Bilateral tubal occlusion
  • Submucous fibroid(s)
  • Diagnosis with increased abortion risk other than fibroid(s)
NRP < 0.05Random: NA
Enrollment period:Groups:Indications:Baseline fibroid size:Miscarriage rate, N (%):Methods and blinding: NA
1997 to 2003G1: Myomectomy before IVF
  • Infertility: 100%
NRG1: 8 (7)Pt selection criteria: ++
Funding:G2: No myomectomy before IVFPre-operative therapy:Type of fibroid:G2: 3 (4)Loss to follow-up: 10–20%
NRN at enrollment:NRNRP = NSDrop-out rates: >10%
G1: 84Associated procedure(s):Delivery rate, N (%):Statistical issues: -
G2: 84NRG1: 21 (25)EXTERNAL VALIDITY: poor (6)
N at follow-up:G2: 10 (12)Age: +, reported
193 enrolledP < 0.05Race: NA, not US study
143 completed the studyModifiers:Pregnancy history: -, NR
25 replaced to reach 168NRSurgical history: -, NR
Followup interval: NRFibroid/uterine size: -
Age, yrs ± SD:Number of fibroids: -
All: 33.04 ± 4.76Location of fibroids: -
G1: 32.83 ± 4.12Baseline characteristics: -, NR
G2: NRLength of follow-up: +
Race/ethnicity:Measurement methods: +
NRMeasurement reliability: +
Parity, parous, N:Clinical care: +
G1: 0
G2: 0
Baseline Hgb/Hct:
NR
Author:Design:Inclusion criteria:Baseline uterine volume:Pregnancy rate, %:Quality:
Casini et al., 2006RCT
  • Infertility ≥ 1yr
  • No other explanation for infertility
  • Age < 35
  • One fibroid
  • ≤ 40mm diameter
NRG1:Overall quality score: fair
Country and setting:Intervention:Exclusion criteria:Number of fibroids:Submucosal: 43.3*INTERNAL VALIDITY: good
Italy, Academic medical centerMyomectomy for unexplained infertility
  • ≥ 2 fibroids
  • Size ≥ 40 mm
  • Body wt. > 20% above normal
  • Use of hormones within 8 wks
OneIntramural: 56.5Random: NA
Enrollment period:Groups:Indications:Baseline fibroid size:Subserosal: no surgeriesMethods and blinding: NA
01/1998 to 04/2005G1: Hysteroscopic or laparoscopic surgeryUnexplained infertilityNRIntramural-subserosal: 35.3Pt selection criteria: +
Funding:G2: No surgeryPre-operative therapy:Type of fibroid:Submucosal-intramural: 36.4*Loss to follow-up: NR
NRN at enrollment:NoneAs per groupsG2:Drop-out rates: NR
G1:Associated procedure(s):Submucosal: 27.2*Statistical issues: +
Submucosal: 30NRIntramural: 40.9EXTERNAL VALIDITY: poor (4)
Intramural: 23Subserosal: 63.6Age: +, reported
Subserosal: no surgeriesIntramural-subserosal: 21.4Race: NA, not US study
Intramural-subserosal: 17Submucosal-intramural: 15.0*Pregnancy history: +, reported
Submucosal-intramural: 22*P < 0.05Surgical history: -, NR
G2:Miscarriage rate, % ,Fibroid/uterine size: -
Submucosal: 22G1:Number of fibroids: -
Intramural: 22Submucosal: 38.5Location of fibroids: +
Subserosal: 11Intramural: 30.8Baseline characteristics: +, reported
Intramural-subserosal: 14Subserosal: no surgeriesLength of follow-up: -
Submucosal-intramural: 20Intramural-subserosal: 33.3Measurement methods: +
N at follow-up:Submucosal-intramural: 50.0Measurement reliability: +
NRG2:Clinical care: +
Age, yrs ± SD:Submucosal: 50.0
NR by group; by fibroid type:Intramural: 33.3
Submucosal: 31.4 ± 2.5Subserosal: 0
Intramural: 32.2 ± 1.9Intramural-subserosal: 66.6
Subserosal: 32.4 ± 2.1Submucosal-intramural: 66.6
Intramural-subserosal: 29.9 ± 1.6P = NR
Submucosal-intramural: 32.2 ± 2.5Modifiers:
Race/ethnicity:NR
NR
Parity:
NR
Baseline Hgb/Hct:
NR
Author:Design:Inclusion criteria:Baseline uterine size:Operative time, min ± SD:Quality:
Dessolle et al., 2001Prospective case series
  • Age 18 to 43 yrs
  • Infertility ≥ 24 mos
  • Intramural or subserous fibroids > 3 cm in diameter
  • < 4 myomas, and largest myoma < 10 cm
NRG1: 150 ± 60Overall quality score: fair
Soriano et al., 2003Intervention:Exclusion criteria:Number of fibroids, mean ± SD:G2: 148 ± 47INTERNAL VALIDITY: fair
Country and setting:Laparoscopic myomectomy
  • Anesthetic contraindications
  • Only submucous fibroids
G1: 1.7 ± 0.6Complications, N:Random: NA
France, CommunityGroups:Indications, N (%):G2: 1.6 ± 0.6G1: 4*Methods and blinding: NA
Enrollment period:G1: Laparoscopic myomectomyPrimary infertility:P = NSG2: 2Pt selection criteria: ++
01/1990 to 10/1988G2: Laparoconversion for myomectomyG1: 28 (31.8)Baseline size of largest fibroid (cm ± SD):Length of stay, days ± SD:Loss to follow-up: NA
Funding:N at enrollment:G2: 6 (33.4)G1: 6.2 ± 1.8G1: 3.0 ± 1Drop-out rates: NA
NRG1: 88Pre-operative therapy:G2: 8.1 ± 1.4G2: 5.5 ± 1Statistical issues: -
G2: 18NoneP < 0.001P < 0.001EXTERNAL VALIDITY: fair (3)
N at follow-up:Associated procedure(s):Type of fibroid, N (%):Pregnancy rate, N (%):Age: +, reported
NRNRSubserosal:G1: 42 (48)Race: NA, not US study
Age, yrs ± SD:G1: 31 (35)G2: 10 (56)Pregnancy history: -, NR
G1: 36.1 ± 2.1G2: 0P = NSSurgical history: -, NR
G2: 34.7 ± 2.4Intramural:Pregnancies, N:Fibroid/uterine size: +
Race/ethnicity:G1: 57 (65)G1: 44Number of fibroids: +
NRG2: 18 (100)G2: 10Location of fibroids: +
Parity:P = NSBaseline characteristics: +, reported
NRSpontaneous pregnancy, N (%):Length of follow-up: ++
Baseline Hgb/Hct:G1: 36/44 (82)Measurement methods: +
NRG2: 8/10 (80)Measurement reliability: -
P = NSClinical care: +
Ovulation induction + IUI, N (%):
G1: 2 (5)
G2: 1 (10)
IVF + ET, N (%):
G1: 6 (13)
G2: 1 (10)
First-trimester miscarriage, N:
G1: 6
G2: 3
Abortion, N:
G1: 2
G2: 2
Dehiscence of uterine scar, N:
G1: 0
G2: 0
Vaginal delivery, N (%):
G1:26/34 (77)
G2: 2/4 (50)
Cesarean delivery, N (%):
G1: 8/34 (24)
G2: 2/4 (50)
Ectopic pregnancy, N:
G1: 1
G2: 0
Live newborn, N (%):
G1: 36/44 (41)
G2: 4/10 (40)
Premature delivery, N:
G1: 0
G2: 1
Time to conception, mos ± SD:
G1: 7.5 ± 2.6
G2: 15.1 ± 2.4
P < 0.001
Patients with unexplained infertility, N (%):
G1: 32/42 (76)
G2: 8/9 (89)
P = NS
Patients with minor infertility factors, N (%):
G1: 10/42 (24)
G2: 2/9 (22)
P = NS
Patients with primary infertility, N (%):
G1: 14/28 (50)
G2: 2/6 (33)
P = NS
Patients with secondary infertility, N (%):
G1: 28/60 (47)
G2: 8/12 (66)
P = NS
Adhesions, N (%):
G1: 12/16 (75)
G2: 4/4 (100)
Recurrence N (%):
G1: 6/66 (9)*
G2: 2/12 (17)
Re-operation (%):
G1: 0
G2: 2
Modifiers:
NR
Author:Design:Inclusion criteria:Baseline uterine size:Operative time range in min:Quality:
Di Gregorio et al., 2001Retrospective case series
  • Women who received myomectomy for symptomatic fibroids, infertility, or “size and/or number of fibroids required surgical treatment”
  • Fibroid size ≥ 10 mm
NR30 to 140Overall quality score: fair
Country and setting:Intervention:Exclusion criteria:Number of fibroids, range:Conversion to laparotomy, N:INTERNAL VALIDITY: fair
Italy, Specialty fibroid treatment centerLaparoscopic myomectomyNR1 to 92/635Random: NA
Enrollment period:Groups:Indications, N:Baseline fibroid size (mm):Adhesions at second look, N (%):Methods and blinding: NA
03/1988 to 04/2001NA
  • Infertility: 445
< 20: 633 (54%)2/121 (1.6)Pt selection criteria: +
Funding:N at enrollment:Preoperative therapy:21 to 39: 357 (30.5%)Modifiers:Loss to follow-up: NA
NR635 patientsNR40 to 59: 123 (10.5%)NRDrop-out rates: NA
(1,170 fibroids)Additional procedures, N:> 60: 57 (4.9%)Statistical issues: -
N at follow-up:
  • Adhesiolysis: 118
  • Ovarian cystectomy: 89
  • Coagulation of endometriotic lesions: 157
  • Salpingectomy for ectopic pregnancy: 5
  • Appendectomy: 5
Type of fibroid, N (%):EXTERNAL VALIDITY: fair (3)
121 second look surgeries
  • Subserous: 630 (53.8)
  • Intramural: 412 (35.2)
  • Pedunculated: 128 (10.9)
Age: -, NR
Age, mean yrs (range):Race: NA, not US study
34.5 (24 to 51)Pregnancy history: +, reported
Race/ethnicity:Surgical history: -, NR
NRFibroid/uterine size: +
Parity, parous (%):Number of fibroids: +
Overall: 278 (43.8)Location of fibroids: +
Baseline Hgb/Hct:Baseline characteristics: -, NR
NRLength of follow-up: NA
Measurement methods: +
Measurement reliability: +
Clinical care: +
Author:Design:Inclusion criteria:Baseline uterine size:Neonates, N (%):Quality:
Dubuisson et al., 2000Retrospective case series
  • Age < 45 years
  • Underwent LM
  • ≥1 subserous or intramural myoma >20 mm in diameter
NR100 of 145 (69%) delivered viable neonatesOverall quality score: poor
Country and setting:Intervention:Exclusion criteria:Number of fibroids, (%):Mode of delivery, N (%):INTERNAL VALIDITY: poor
France, Academic medical centerLaparoscopic myomectomyNR1: 60 (61)Spontaneous vaginal delivery:Random: NA
Enrollment period:Groups:Indications, N (%):2: 18 (18)36 (36)Methods and blinding: NA
03/1989 to 12/1996NA
  • Infertility/recurrent spontaneous abortion: 53 (54)
  • Pain/pressure: 29 (29.6)
  • Abnormal bleeding: 16 (16.3)
  • Rapidly growing myoma: 14 (14.3)
≥3: 20 (21)Forceps delivery: 22 (22)Pt selection criteria: +
Funding:N at enrollment:Pre-operative therapy:Baseline largest fibroid size, mm ± SD:C-section during labor: 14 (14)Loss to follow-up: 10–20%
NR263NR47.8 ± 20.6C-section before labor: 28 (28)Drop-out rates: NA
Number of women at follow-up, N (%):Associated procedure(s):Type of largest fibroid, (%):Gestational age, weeks ± SD:Statistical issues: -
98 (37.2)NRIntramural: 32 (32.6)36.5 ± 2.7EXTERNAL VALIDITY: poor (4)
145 pregnancies/ 100 delivered viable neonates;Subserous: 41 (41.8)Birth weight, kg ± SD:Age: +, reported
Data presented here is on 100 neonatesPedunculated: 25 (25.6)3.2 ± .06Race: NA, not US study
No pregnancy during follow-up after LM:1-min Apgar score, SD:Pregnancy history: +, reported
128 (48.7)8.9 ±2.0Surgical history: -, NR
Lost to follow-upPremature delivery, N (%):Fibroid/uterine size: -
37 (14.1)14 (14)Number of fibroids: -
Age, yrs ± SD:Indications for C-section after LM, N (%):Location of fibroids: -
33.2 ± 4.0Elective C-section of uterine scar: 16/42 (38.1)Baseline characteristics: +, reported
Race/Ethnicity:Failed trial of labor,: 14 (33.3)Length of follow-up: ++
NRMaternal/fetal pathology: 6 (14.3)Measurement methods: +
Parity, parous, N (%):Breech presentation: 3 (7.1)Measurement reliability: +
Nullipara: 78 (79)Suspected uterine rupture: 3 (7.1)Clinical care: +
Primipara: 9 (9)Uterine rupture on LM scar, N (%):
Multipara: 11 (12)1 (2.4)
Baseline Hgb/Hct:Uterine rupture away form LM scar, N (%):
NR2 (4.8)
Obstetric complications, N (%):
Uterine rupture: 3 (3)
Uterine rupture related to LM: 1 (1)
Postpartum hemorrhage: 3 (3)
Rate of uterine rupture: 1.0% (95% CI 0.0–5.5)
Modifiers:
NR
Author:Design:Inclusion criteria:Baseline uterine size:Operative time, min ± SD:Quality:
Kumakiri et al., 2005Retrospective case series
  • Menorrhagia and abdominal fullness
  • Infertility
  • Fibroids ≥ 5 cm
  • Wishing to have children
  • Largest fibroid ≤ 12 cm
  • Uterus size ≤ 14 weeks gestation
NRPregnancy: 105.3 ± 45.3Overall quality score: fair
Country and setting:Intervention:Exclusion criteria:Number of fibroids enucleated, mean ± SD:No pregnancy: 106.0 ± 51.5INTERNAL VALIDITY: fair
Japan, Academic medical centerLaparoscopic myomectomySee inclusion criteriaPregnancy: 3.2 ± 2.7P =0.75Random: NA
Enrollment period:Groups:Indications, N:No pregnancy: 3.7 ± 3.6Mean estimated blood loss, ml ± SD:Metods and blinding: NA
01/1998 to 12/2002NAInfertility: 59P = 0.04Pregnancy: 85.2 ± 105.8Pt selection criteria: +
Funding:N at enrollment:Menorrhagia: 20Baseline largest fibroid size mm ± SD:No pregnancy: 120.3 ± 174.5Loss to follow-up: <10%
NR108Dysmenorrhea: 17Pregnancy: 67.5 ± 16.9P =0.53Drop-out rates: NA
N at follow-up:Lower abdominal pain: 6No pregnancy: 62.3 ± 16.3Pregnancy success rate, N (%):Statistical issues: -
NAOther: 6P = 0.00440/108 (37%)EXTERNAL VALIDIT: fair (2)
Age, yrs ± SD:Pre-operative therapy (%):Type of fibroid:Spontaneous pregnancies, N (%):Age: +, reported
35.5 ± 3.5GnRH: 86 (79.6)NR40/47 (85.1)Race: NA, not US study
Race/Ethnicity:Associated procedure(s):ART pregnancies, N (%);Pregnancy history: -, NR
NANR7/47 (14.9)Surgical history: -, NR
Parity, parous (N):Miscarriages, N (%):Fibroid/uterine size: +
Multiparous: 1011/47 (23.4)Number of fibroids: +
Baseline Hgb/Hct:Ectopic, N:Location of fibroids: +
NR1/47 (2.1)Baseline characteristics: +, reported
Live births, N (%):Length of follow-up: +
32/47 (68.1)Measurement methods: +
Elective Cesarean delivery, N (%):Measurement reliability: +
9/32 (28.1)Clinical care: +
VBALM failure, N (%):
4/23 (17.4)
Modifiers:
Pregnancy rate correlated positively with diameter of largest fibroid:
OR =1.06; 95% CI, 1.02–1.10
P = 0.004
Modifiers:
Pregnancy rate correlated negatively with age at myomectomy:
OR = 0.88; 95% CI, 0.80–0.98
P = 0.02
Pregnancy rate correlated negatively with number of enucleated fibroids:
OR =1.17; 95% CI, 1.01–1.37
P = 0.04
Author:Design:Inclusion criteria:Baseline uterine size:Operative time, mean min (range):Quality:
Malzoni et al., 2003Retrospective case series
  • Undergoing laparoscopic myomectomy
NR85 (58 to 180)Overall quality score: fair
Country and setting:Intervention:Exclusion criteria:Fibroids removed, N (%):Conversion to laparotomy, N (%):INTERNAL VALIDITY: fair
Italy, CommunityLaparoscopic myomectomy for fibroids ≥ 5cmNR1: 84 (58.33)2 (1.39)Random: NA
Enrollment period:Groups:Indications, N (%):2: 35 (24.3)Transfusion, N (%):Methods and blinding: NA
01/1997 to 07/1999NA
  • Infertility: 102 (70.8)
  • Abnormal bleeding: 98 (68)
  • Pain: 64 (44.4)
  • More than 1 symptom: 81 (56.2)
3: 17 (11.8)1 (0.69)Pt selection criteria: +
Funding:N at enrollment:Pre-operative therapy:4: 6 (4.17)Length of stay, days (range):Loss to follow-up: NA
NR144NoneBaseline dominant fibroid size, mean cm (range):2.6 (2 to 5)Drop-out rates: NA
N at follow-up:Associated procedure(s), N (%):7.8 (5 to 18)Intramural hematoma, N (%):Statistical issues: -
NR
  • Lysis: 24 (16.6)
  • Tubal plasty: 6 (4.16)
  • Appendectomy: 5 (3.47)
  • Ovarian cystectomy: 4 (2.77)
  • Coagulation of endometriosis: 3 (2.08)
Type of fibroid, N (%):1 day post-op: 108 (75)EXTERNAL VALIDITY: fair (1)
Age, mean yrs:
  • Interstitial submucous: 108 (75)
  • Subserous sessile: 15 (10.4)
  • Pedunculated: 7 (4.86)
  • Intraligamentous: 14 (9.7)
2 day post-op: 14 (9.7)Age: +, reported
33.7 (22 to 41)Pregnancy rate N (%)*:Race: NA, not US study
Race/ethnicity:26 in 21 patients (25%)Pregnancy history: +, reported
NRSpontaneous: 20Surgical history: -, NR
Parity, parous, N (%):After IVF: 1Fibroid/uterine size: +
Nulligravida: 98 (60.5)Live birth, N:Number of fibroids: +
Baseline Hgb/Hct:21Location of fibroids: +
NRCesarean delivery, N:Baseline characteristics: +, reported
12/21Length of follow-up: +
Vaginal delivery, N:Measurement methods: +
9/21Measurement reliability: +
Uterine rupture, N:Clinical care: +
0
Miscarriage, N:
4/26
Ectopic pregnancy, N:
1/26
Pregnancy rate, 1997, N (%):
6-mon: 13/38 (34.21)
12-mon: 21/38 (55.26)
Adhesions at 2nd-look, N (%):
6/18 (33)
Severity of adhesions, N (%):
Type 1: 4 (22.2)
Type 2: 2 (11.1)
Type 3: 0
Modifiers:
NR
Author:Design:Inclusion criteria:Baseline uterine size:Operative time, min ± SD:Quality:
Seracchioli et al., 2000RCT
  • Fibroid(s) ≥ 5 cm
  • Infertility
NRG1: 88.85 ± 26.91Overall quality score: fair
Country and setting:Intervention:Exclusion criteria:Number of fibroids, mean ± SD:G2: 100.23 ± 38.34INTERNAL VALIDITY: fair
Italy, Academic medical centerMyomectomy
  • Pedunculated fibroids
  • Uterine size above umbilicus
  • > 3 fibroids of > 5 cm size
  • Other causes of infertility
G1: 2.75 ± 1.98Conversion to laparotomy, N (%):Random: +
Enrollment period:Groups:Indications for LM, N (%):G2: 2.94 ± 1.53G1: NAMethods and blinding: NA
01/1993 to 01/1998G1: Abdominal myomectomy
  • Primary infertility: 87 (66.4)
  • Secondary infertility: 44 (33.6)
Baseline size of largest fibroid (cm ± SD):G2: 3 (4.3)Pt selection criteria: ++
Funding:G2: Laparoscopic myomectomyPreoperative therapy:G1: 7.47 ± 2.60Intra-operative complications:Loss to follow-up: 10–20%
NRN at enrollment:NoneG2: 7.07 ± 2.54NoneDrop-out rates: NA
G1: 65Associated procedure(s):Type of fibroid, N (%):Decrease in Hgb:Statistical issues: +
G2: 66NRSubserosal:G1: 2.17 ± 1.57EXTERNAL VALIDITY: fair (1)
N at follow-up:G1: 19 (44.2)G2: 1.33 ± 1.23Age: +, reported
G1: 59G2: 24 (55.8)P < 0.001Race: NA, not US study
G2: 56Intramural:Transfusion, N:Pregnancy history: +, reported
Age, yrs ± SD:G1: 54 (52.9)G1: 3Surgical history: -, NR
G1: 33.97 ± 4.79G2: 48 (47.1)G2: 0Fibroid/uterine size: +
G2: 34.00 ± 4.11“Reaching Cavity”:Fever > 38° C, N (%):Number of fibroids: +
Race/ethnicity:G1: 5 (9.2)G1: 17 (26.2)Location of fibroids: +
NRG2: 2 (4.1)G2: 8 (12.1)Baseline characteristics: +, reported
Parity:Length of stay, hrs ± SD:Length of follow-up: +
See fertility statusG1: 142.80 ± 34.60Measurement methods: +
Baseline Hgb/Hct:G2: 75.61 ± 37.09Measurement reliability: +
NRAntibiotic Rx, N (%):Clinical care: +
G1: 17 (26.2)
G2: 8 (12.1)
Pregnancy rate, N (%):
G1: 33/59 (55.9)
G2: 30/56 (53.6)
Miscarriage, N (%):
G1: 4 (12.1)
G2: 6 (20.0)
Ectopic:
G1: 0
G2: 1
Births:
G1: 27/59
G2: 20/56
Preterm births, N (%):
G1: 2 (7.4)
G2: 1 (5.0)
Cesarean rate, N (%):
G1: 21 (77.8)
G2: 13 (65.0)
Uterine Rupture:
0
Fibroid recurrence, by US every 6 mos, N (%):
G1: 12 (20.3)
G2: 12 (21.4)
Subsequent treatment, N:
G1:
Myomectomy: 3
Hysterectomy: 1
G2: 0
Modifiers:
NR
*

Calculated by reviewer.

From: Appendix C. Evidence Tables

Cover of Management of Uterine Fibroids
Management of Uterine Fibroids: An Update of the Evidence.
Evidence Reports/Technology Assessments, No. 154.
Viswanathan M, Hartmann K, McKoy N, et al.

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