An Overview of Uterine Factors That Influence Implantation

Size: px

Start display at page:

Download "An Overview of Uterine Factors That Influence Implantation"

Debra Hood
5 years ago
Views:

1 An Overview of Uterine Factors That Influence Implantation Bulent Urman, M.D. Dept. of Obstetrics and Gynecology Koc University School of Medicine Assisted Reproduction Unit, American Hospital, ISTANBUL

3 Uterine factors that influence implantation Structural uterine anomalies Polyps and fibroids Hydrosalpinx Adenomyosis Chronic Endometritis The cases of endometrial injury and hysteroscopy Thin endometrium

4 Structural uterine anomalies Arcuate uterus Septate uterus Dysmorphic uterus Unicornuate, bicornuate, didelphyic

5 The impact of septate and subseptate/arcuate uteri on the success of IVF From Tomazevic et al. RBM Online 2010

6 Prevalence of uterine anomalies and their impact on early pregnancy in women conceiving after assisted reproduction treatment Jayaprakasan et al. Ultrasound Obstet Gynecol 2011

7 Structural uterine anomalies No randomized study evaluated the effect of hysteroscopic correction on PR either spontaneously or with IVF

8 Dysmorphic uterus

9 Dysmorphic uterus Problems with universal agreement on the diagnosis What is the appropriate treatment? What is the impact of hysteroscopic cavity enlarging procedures on uterine volume, endometrial receptivity and PR?

10 Grading the evidence

11 Endometrial polyps The mechanism by which EPs may affect fertility in ART is also unclear If an EP is detected during an ART cycle, various management options have been reported, including: expectant management cancelation of the cycle and embryo cryopreservation polypectomy and transfer in a subsequent cycle polypectomy without cycle cancelation.

12 Endometrial polyps The evidence regarding the effectiveness of polypectomy prior to ART treatment remains insufficient and demands further research It is generally accepted that small polyps (<10 mm) are not deterimental to ART outcome Larger polyps should be removed

13 FIBROIDS

14 Am J Obstet Gynecol 2008

15 The effect of non-cavity-distorting fibroids on IVF outcome From Sunkara et al. Hum Reprod 2010

16 The effect of non-cavity-distorting fibroids on IVF outcome-first treatment cycles only! From Sunkara et al. Hum Reprod 2010

17 Effect of fibroid removal

18 Hydrosalpinx

19 Effect of untreated hydrosalpinx of 14 studies Camus et al, 1999

20 Effect of removal of hydrosalpinx Odds of pregnancy = 1.75 ( ) Odds of ongoing pregnancy = 2.13 ( ) Embryo implantation = 1.34 ( ) Ectopic pregnancy=0.42 ( ) Miscarriage=0.49 ( ) Cochrane review Johnson et al. 2002

21 Hydrosalpinx and salpingectomy Laparoscopic surgical treatment should be considered for all women with hydrosalpinx who are scheduled to undergo IVF Tubal occlusion and salpingectomy show similar efficacy. Whenever laparoscopy is not recommended for the presence of pelvic adhesions, Essure seems to be the most effective option for management of hydrosalpinx before IVF. Transvaginal aspiration and tubal sclerotherapy are available alternatives but their effectiveness is limited by the high recurrence rate of hydrosalpinx following treatment.

22 Adenomyosis Universal agreement on diagnosis?? USG Doppler MRI

23 Adenomysosis and outcome of IVFclinical pregnancy rates From Vercellini et al. Hum Reprod 2014

24 Adenomysosis and outcome of IVFmiscarriage rates From Vercellini et al. Hum Reprod 2014

25 Asymptomatic adenomyosis and outcome of IVF From Benaglia et al. RBM Online 2014

26 Detrimental effect of adenomyosis and potential improvement with GnRHa Galliano et al. HRU 2015

27 Chronic endometritis A representative photomicrograph of CD138+ PC (a, solid arrows) and CD20+ B-cell (b) infiltration in the human endometrium with CE. Note that endometrial epithelial cells physiologically express CD138 mainly on the basal side of the plasma membranes (a, open arrows).

28 Pathogenesis of CE From Kitaya et al. Am J Reprod Immunol 2016

29 Diagnosis Hysteroscopy endometrial biopsy immunohistochemical staining for plasma cells

30 Does it really exist? Is it a distinct clinical entity or an incidental finding? Is there a proven specific treatment for the condition?

31 Chronic endometritis-outcome after treatment Live birth rate From Cicinelli et al. HR 2015

Chronic endometritis is a significant finding in patients with RIF and should be treated Group 1-Patients with chronic endometritis (confirmed by immunohystochemistry)

32 Chronic endometritis is a significant finding in patients with RIF and should be treated Group 1-Patients with chronic endometritis (confirmed by immunohystochemistry) on biopsy Group 2-Patients who did not have chronic endometritis Group 3-Patients who did not undergo endometrial biopsy From Johnston-McAnanny et al. Fertil Steril 2010

33 Chronic endometritis has no effect on IVF outcome! From Kasius et al. Fertil Steril 2012

34 Endometrial injury and/or hysteroscopy Endometrial injury YES NO From Potdar et al. RBM Online 2012

35 Does local injury to the endometrium before IVF cycle really affect treatment outcome? Results of a randomized placebo controlled trial Baum et al. Gynecol Endocrinol 2012

36 The effect of endometrial injury on ongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization: a randomized controlled trial From Yeung et al. Human Reproduction 2014

39 Hysteroscopy Before the first IVF cycle in all women In women with implantation failure regardless of US findings Only in women with abnormal ultrasound findings

40 Fertility enhancing effects of hysteroscopy Dilatation of the cervical canal Facilitation of an otherwise difficult ET Evaluation of the cavity Treatment of lesions if present Fertility enhancement due to instrumentation at hysteroscopy

41 Is it cost effective to do hysteroscopy in every patient undergoing IVF?

Hysteroscopy improves implantation regardless of abnormal findings

an intracavitary lesion is corrected Uterine instrumentation during

an immunological reaction that involves the release of cytokines and

implantation COST EFFECTIVE 2000 Euro per additional live birth NOT

42 Hysteroscopy improves implantation regardless of abnormal findings Endometrial injury effect Hysteroscopy improves implantation only if an intracavitary lesion is corrected Uterine instrumentation during hysteroscopy could cause a degree of endometrial injury and provoke an immunological reaction that involves the release of cytokines and growth factors, which in turn may influence the likelihood of implantation COST EFFECTIVE 2000 Euro per additional live birth NOT COST EFFECTIVE Euro per additional live birth From Kasius et al. Hum Reprod 2011

43 Hunches are usually wrong, hunches of expert authorities in the field are usually wrong as well Piet Borst WE NEED EVIDENCE

44 RBM Online 2013

46 Problems associated with hysteroscopic cavity evaluation Inter/intra-observer agreement regarding both normal and abnormal findings The significance of abnormal findings is not clear Whether treatment improves implantation rates is unknown

47 Observer agreement in the evaluation of the uterine cavity prior to IVF From Kasius et al. Hum Reprod 2011

48 Agreement on the diagnosis of septate uterus From Smit et al. Fertil Steril 2013 Seventy-eight observers from 24 different countries assessed 8 hysteroscopy recordings. The interobserver agreement on uterine shape variations septate and arcuate was fair (intraclass correlation coefficient ). The agreement among international experts on the hysteroscopic diagnosis of the septate uterus was found to be poor.

49 Hysteroscopy in couples with implantation failure

50 Endometrial injury and/or hysteroscopy From Potdar et al. RBM Online 2012

52 TROPHY Study RCT 700 couples with 2-4 failed cycles randomized to hysteroscopy or no hysteroscopy in the cycle preceding IVF Live birth rate Hysteroscopy group 31% No hysteroscopy group 29% From El Thouky et al. ESHRE 2014

53 Endometrial thickness Figure 2: Difference in means and 95% confidence intervals 0.4 mm Figure 3: Odds ratio and 95% confidence intervals OR=1.4 ( ) Momeni et al. J Hum Reprod Sci 2011

54 Other factors Molecular factors that affect receptivity Receptive vs nonreceptive endometrium-gene expression profiles Deciudual phenotype What happens in extreme cases??

Surgery and Infertility

Surgery and Infertility Dr Phill McChesney BHB MBChB FRANZCOG MRMed CREI Laparoscopy Prior to Considering IVF Diagnostic Tubal Surgery Treatment of peritubal adhesions Reconstructive surgery Sterilization