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MANAGEMENT OF
THIN ENDOMETRIUM
An evidence-based
Guidelines
Canadian Fertility and
Andrology Society 2019
Prof. Aboubakr
Elnashar
Benha University Hospital,
Egypt
ABOUBAKR ELNASHAR
CONTENTS
 INTRODUCTION
I. MEASUREMENT
II. INCIDENCE
III.CAUSES
IV.IMPACT & TREATMENT
1.OVARIAN STIMULATION
2.FRESH EMBRYO TRANSFER
3.FROZEN EMBRYO TRANSFER
 CONCLUSION
ABOUBAKR ELNASHAR
INTRODUCTION
 Assessment of the endometrium is an essential
component in ART.
 En th:
 has been identified as a prognostic factor for
success in ART.
 When the endometrium is assessed to be ‘thin
 physicians and patients face a decision of
 Whether or not to proceed with the treatment
cycle?.
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR
 Certainty of the evidence (GRADE)
⨁⨁⨁⨁ HIGH
⨁⨁⨁◯ MODERATE
⨁⨁◯◯ LOW
⨁◯◯◯ VERY LOW
 High quality:
 We are very confident that the true effect lies close to that of the
estimate of the effect
 Moderate quality:
 We are moderately confident in the effect estimate: The true effect is
likely to be close to the estimate of the effect, but there is a
possibility that it is substantially different
 Low quality:
 Our confidence in the effect estimate is limited: The true effect may
be substantially different from the estimate of the effect
 Very low quality:
 We have very little confidence in the effect estimate: The true effect
is likely to be substantially different from the estimate of effect
ABOUBAKR ELNASHAR
I. MEASUREMENTS
 The endometrium should be measured transvaginally
in the sagittal plane at the thickest portion near the
fundus.
 Strong
 ⊕○○○
 Recommendation is based on commonly accepted
practice and to
 ensure consistency in measurements
 aid in clinical assessment,
research and reporting.
ABOUBAKR ELNASHAR
 Repeat any thin endometrium measurement.
 Weak
 ⊕○○○
 Recommendation is based on
 commonly accepted practice and
 intra-observer variability.
 Uterine contractions
 changes in endometrial thickness of up to 3–4 mm due to changes in
the myometrium and subendometrium.
 Most patients have multiple contractions per minute.
 Periodicity tends to differ with stage of cycle, circulating oestradiol and
progesterone concentrations, and endometrial thickness/pattern
(Dastidar and Dastidar, 2003; Pierson, 2018).
 strict adherence to proper technique
 wait for the wave to pass and measure again
(Pierson, 2018).
ABOUBAKR ELNASHAR
 Thin endometrium in ART is often defined as
 En th <7 mm or <8 mm.
ABOUBAKR ELNASHAR
 Various factors can limit the accuracy of endometrial
measurements such as:
 fibroids,
 adenomyosis,
 polyps,
 uterine orientation,
 body habitus,
 previous surgeries,
 uterine contractions,
 ultrasound machine quality,
 interobserver and intra-observer variability, and
 patient intolerance.
 ⊕⊕○○
ABOUBAKR ELNASHAR
II. INCIDENCE
 Ovarian stimulation cycles: as high as 38–66%
 IVF: between 1% and 2.5%.
⊕⊕○○
 Based on retrospective and prospective observational
studies.
 These are likely to underestimate the true incidence
of thin endometrium as they do not include cancelled
cycles.
ABOUBAKR ELNASHAR
III. CAUSES
 Asherman syndrome,
 History of uterine surgery
 Infection
 Radiation
 Although the incidence of thin endometrium in these
scenarios is unclear.
⊕○○○
 Retrospective case series show an association of thin
endometrium with the risk factors listed.
ABOUBAKR ELNASHAR
IV. IMPACT AND TREATMENT
1. OVARIAN STIMULATION CYCLES
 Thin endometrium may not impact pregnancy
outcomes in ovarian stimulation treatment cycles.
 ⊕○○○
 Most observational studies do not show a difference
in PR with thin endometrium at different cut-offs.
 A systematic review did not find a difference in En T
in patients who were pregnant versus not pregnant.
ABOUBAKR ELNASHAR
 Patients undergoing ovarian stimulation with thin
endometrium may be counselled that the effect on
pregnancy rates is unclear.
 Weak
 ⊕○○○
 Most observational studies do not show a difference
in PR with thin endometrium at different cut-offs.
 A systematic review did not find a difference in En th
in patients undergoing ovarian stimulation who were
pregnant versus not pregnant.
ABOUBAKR ELNASHAR
 In ovarian stimulation treatment cycles, there is
insufficient evidence to recommend changing
stimulation medications or a specific stimulation
medication.
 Weak
 ⊕○○○
 There are insufficient studies evaluating the effect of
specific ovarian stimulation protocols for patients with
thin endometrium.
ABOUBAKR ELNASHAR
 In ovarian stimulation treatment cycles, there is
insufficient evidence to recommend the use of
adjuvants to improve En th or PR
 Weak
 ⊕○○○
 There are insufficient studies evaluating the effect of
adjuvants in ovarian stimulation protocols for patients
with thin endometrium.
ABOUBAKR ELNASHAR
2. FRESH IVF-ET CYCLES,
 Patients should be counselled that En th <8 mm may
have a negative impact on PR and LBR.
 Strong
 ⊕⊕○○
 Observational studies consistently demonstrate lower
PR in fresh IVF cycles with En T <8 mm.
ABOUBAKR ELNASHAR
 In fresh IVF-embryo transfer cycles, patients with thin
endometrium can be offered elective cryopreservation
of embryos and transfer in a subsequent cycle.
 Weak
 ⊕○○○
 One poorly designed small observational study found
lower PR with fresh embryo transfer compared with
cryopreservation and transfer in a subsequent cycle.
ABOUBAKR ELNASHAR
 In patients with thin endometrium undergoing embryo
transfer cycles, we suggest against the use of aspirin
to improve pregnancy rates.
 Weak
 ⊕○○○
 No effect in one small RCT.
ABOUBAKR ELNASHAR
 In patients with thin endometrium undergoing fresh
IVF-embryo transfer cycles, we suggest against the
use of luteal oestradiol to improve pregnancy rates.
 Weak
 ⊕○○○
 No benefit seen in one small observational study.
ABOUBAKR ELNASHAR
 In patients with thin endometrium undergoing embryo
transfer cycles, there is insufficient evidence to
recommend the use of sildenafil to improve
pregnancy rates.
 Weak
 ⊕○○○
 No improvement in PR seen in poorly designed RCT;
however, there was an improvement in endometrial
thickness.
ABOUBAKR ELNASHAR
 In patients with thin endometrium undergoing embryo
transfer cycles, we suggest against the use of
intrauterine infusion of G-CSF to improve pregnancy
rates.
 Weak
 ⊕⊕○○
 No benefit for clinical pregnancy or LBR in
observational data or one RCT.
 Potential side effects and complications with G-CSF
intrauterine infusion also need to be further studied.
 G-CSF intrauterine infusion may improve endometrial
thickness based on observational data.
ABOUBAKR ELNASHAR
 In patients with thin endometrium undergoing embryo
transfer cycles, we suggest against the use of
 pentoxifylline,
 HCG,
 gonadotropin-releasing hormone agonists,
 platelet-rich plasma or
 stem cells to improve pregnancy rates.
 Weak
 ⊕○○○
 Only case reports and case series are in the
literature, with no controlled studies reported.
 Further research to evaluate the potential risks and
benefits of these adjuvants is needed.
ABOUBAKR ELNASHAR
3. FROZEN IVF-EMBRYO TRANSFER CYCLES
 Patients should be counselled that endometrial
thickness <7 mm may have a negative impact on PR
and LBR.
 Strong
 ⊕⊕○○
 Observational study demonstrates lower PR in frozen
IVF-embryo transfer cycles with endometrial
thickness <7 mm.
 Oocyte donation studies did not show an impact on
PR
ABOUBAKR ELNASHAR
 For patients with a history of thin endometrium in ART
treatment undergoing endometrial preparation for
embryo transfer, there is insufficient evidence that
any specific protocol (natural cycle or hormone
replacement) for endometrial preparation provides
better pregnancy outcomes.
 Weak
 ⊕○○○
 There are no studies which compare different
endometrial preparation protocols for frozen embryo
transfers.
ABOUBAKR ELNASHAR
CONCLUSIONS
 Thin endometrium is an infrequent but challenging
occurrence in assisted reproduction.
 Physicians must balance the prognosis for patients if
they proceed with treatment with a thin endometrium
or consider alternative treatments.
 Currently, there is minimal evidence to support any
specific protocols or adjuvants to significantly improve
pregnancy outcomes in patients with thin
endometrium.
ABOUBAKR ELNASHAR

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Thin Endometrium

  • 1. MANAGEMENT OF THIN ENDOMETRIUM An evidence-based Guidelines Canadian Fertility and Andrology Society 2019 Prof. Aboubakr Elnashar Benha University Hospital, Egypt ABOUBAKR ELNASHAR
  • 2. CONTENTS  INTRODUCTION I. MEASUREMENT II. INCIDENCE III.CAUSES IV.IMPACT & TREATMENT 1.OVARIAN STIMULATION 2.FRESH EMBRYO TRANSFER 3.FROZEN EMBRYO TRANSFER  CONCLUSION ABOUBAKR ELNASHAR
  • 3. INTRODUCTION  Assessment of the endometrium is an essential component in ART.  En th:  has been identified as a prognostic factor for success in ART.  When the endometrium is assessed to be ‘thin  physicians and patients face a decision of  Whether or not to proceed with the treatment cycle?. ABOUBAKR ELNASHAR
  • 5.  Certainty of the evidence (GRADE) ⨁⨁⨁⨁ HIGH ⨁⨁⨁◯ MODERATE ⨁⨁◯◯ LOW ⨁◯◯◯ VERY LOW  High quality:  We are very confident that the true effect lies close to that of the estimate of the effect  Moderate quality:  We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low quality:  Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect  Very low quality:  We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect ABOUBAKR ELNASHAR
  • 6. I. MEASUREMENTS  The endometrium should be measured transvaginally in the sagittal plane at the thickest portion near the fundus.  Strong  ⊕○○○  Recommendation is based on commonly accepted practice and to  ensure consistency in measurements  aid in clinical assessment, research and reporting. ABOUBAKR ELNASHAR
  • 7.  Repeat any thin endometrium measurement.  Weak  ⊕○○○  Recommendation is based on  commonly accepted practice and  intra-observer variability.  Uterine contractions  changes in endometrial thickness of up to 3–4 mm due to changes in the myometrium and subendometrium.  Most patients have multiple contractions per minute.  Periodicity tends to differ with stage of cycle, circulating oestradiol and progesterone concentrations, and endometrial thickness/pattern (Dastidar and Dastidar, 2003; Pierson, 2018).  strict adherence to proper technique  wait for the wave to pass and measure again (Pierson, 2018). ABOUBAKR ELNASHAR
  • 8.  Thin endometrium in ART is often defined as  En th <7 mm or <8 mm. ABOUBAKR ELNASHAR
  • 9.  Various factors can limit the accuracy of endometrial measurements such as:  fibroids,  adenomyosis,  polyps,  uterine orientation,  body habitus,  previous surgeries,  uterine contractions,  ultrasound machine quality,  interobserver and intra-observer variability, and  patient intolerance.  ⊕⊕○○ ABOUBAKR ELNASHAR
  • 10. II. INCIDENCE  Ovarian stimulation cycles: as high as 38–66%  IVF: between 1% and 2.5%. ⊕⊕○○  Based on retrospective and prospective observational studies.  These are likely to underestimate the true incidence of thin endometrium as they do not include cancelled cycles. ABOUBAKR ELNASHAR
  • 11. III. CAUSES  Asherman syndrome,  History of uterine surgery  Infection  Radiation  Although the incidence of thin endometrium in these scenarios is unclear. ⊕○○○  Retrospective case series show an association of thin endometrium with the risk factors listed. ABOUBAKR ELNASHAR
  • 12. IV. IMPACT AND TREATMENT 1. OVARIAN STIMULATION CYCLES  Thin endometrium may not impact pregnancy outcomes in ovarian stimulation treatment cycles.  ⊕○○○  Most observational studies do not show a difference in PR with thin endometrium at different cut-offs.  A systematic review did not find a difference in En T in patients who were pregnant versus not pregnant. ABOUBAKR ELNASHAR
  • 13.  Patients undergoing ovarian stimulation with thin endometrium may be counselled that the effect on pregnancy rates is unclear.  Weak  ⊕○○○  Most observational studies do not show a difference in PR with thin endometrium at different cut-offs.  A systematic review did not find a difference in En th in patients undergoing ovarian stimulation who were pregnant versus not pregnant. ABOUBAKR ELNASHAR
  • 14.  In ovarian stimulation treatment cycles, there is insufficient evidence to recommend changing stimulation medications or a specific stimulation medication.  Weak  ⊕○○○  There are insufficient studies evaluating the effect of specific ovarian stimulation protocols for patients with thin endometrium. ABOUBAKR ELNASHAR
  • 15.  In ovarian stimulation treatment cycles, there is insufficient evidence to recommend the use of adjuvants to improve En th or PR  Weak  ⊕○○○  There are insufficient studies evaluating the effect of adjuvants in ovarian stimulation protocols for patients with thin endometrium. ABOUBAKR ELNASHAR
  • 16. 2. FRESH IVF-ET CYCLES,  Patients should be counselled that En th <8 mm may have a negative impact on PR and LBR.  Strong  ⊕⊕○○  Observational studies consistently demonstrate lower PR in fresh IVF cycles with En T <8 mm. ABOUBAKR ELNASHAR
  • 17.  In fresh IVF-embryo transfer cycles, patients with thin endometrium can be offered elective cryopreservation of embryos and transfer in a subsequent cycle.  Weak  ⊕○○○  One poorly designed small observational study found lower PR with fresh embryo transfer compared with cryopreservation and transfer in a subsequent cycle. ABOUBAKR ELNASHAR
  • 18.  In patients with thin endometrium undergoing embryo transfer cycles, we suggest against the use of aspirin to improve pregnancy rates.  Weak  ⊕○○○  No effect in one small RCT. ABOUBAKR ELNASHAR
  • 19.  In patients with thin endometrium undergoing fresh IVF-embryo transfer cycles, we suggest against the use of luteal oestradiol to improve pregnancy rates.  Weak  ⊕○○○  No benefit seen in one small observational study. ABOUBAKR ELNASHAR
  • 20.  In patients with thin endometrium undergoing embryo transfer cycles, there is insufficient evidence to recommend the use of sildenafil to improve pregnancy rates.  Weak  ⊕○○○  No improvement in PR seen in poorly designed RCT; however, there was an improvement in endometrial thickness. ABOUBAKR ELNASHAR
  • 21.  In patients with thin endometrium undergoing embryo transfer cycles, we suggest against the use of intrauterine infusion of G-CSF to improve pregnancy rates.  Weak  ⊕⊕○○  No benefit for clinical pregnancy or LBR in observational data or one RCT.  Potential side effects and complications with G-CSF intrauterine infusion also need to be further studied.  G-CSF intrauterine infusion may improve endometrial thickness based on observational data. ABOUBAKR ELNASHAR
  • 22.  In patients with thin endometrium undergoing embryo transfer cycles, we suggest against the use of  pentoxifylline,  HCG,  gonadotropin-releasing hormone agonists,  platelet-rich plasma or  stem cells to improve pregnancy rates.  Weak  ⊕○○○  Only case reports and case series are in the literature, with no controlled studies reported.  Further research to evaluate the potential risks and benefits of these adjuvants is needed. ABOUBAKR ELNASHAR
  • 23. 3. FROZEN IVF-EMBRYO TRANSFER CYCLES  Patients should be counselled that endometrial thickness <7 mm may have a negative impact on PR and LBR.  Strong  ⊕⊕○○  Observational study demonstrates lower PR in frozen IVF-embryo transfer cycles with endometrial thickness <7 mm.  Oocyte donation studies did not show an impact on PR ABOUBAKR ELNASHAR
  • 24.  For patients with a history of thin endometrium in ART treatment undergoing endometrial preparation for embryo transfer, there is insufficient evidence that any specific protocol (natural cycle or hormone replacement) for endometrial preparation provides better pregnancy outcomes.  Weak  ⊕○○○  There are no studies which compare different endometrial preparation protocols for frozen embryo transfers. ABOUBAKR ELNASHAR
  • 25. CONCLUSIONS  Thin endometrium is an infrequent but challenging occurrence in assisted reproduction.  Physicians must balance the prognosis for patients if they proceed with treatment with a thin endometrium or consider alternative treatments.  Currently, there is minimal evidence to support any specific protocols or adjuvants to significantly improve pregnancy outcomes in patients with thin endometrium. ABOUBAKR ELNASHAR