Asherman Syndroom Behandeling in Nederland Het Effect van Centralisatie 2003-2013 Mark Hans Emanuel MD PhD Miriam Hanstede MD VVOG maart 2014 Spaarne Ziekenhuis Haarlem/Heemstede/Hoofddorp Universiteit van Amsterdam en Vrije Universiteit

VVOG 2014 Mark Hans Emanuel m@emanuel.nl Belangenverstrengeling Geen in relatie tot het onderwerp van de voordracht VVOG 2014 Mark Hans Emanuel m@emanuel.nl

VVOG 2014 Mark Hans Emanuel m@emanuel.nl Asherman Syndrome Fritsch N=1 1894 Bass N=20 1927 Stamer N=24 1946 Asherman N=29 1948 I would like to take you back to 1894 when Heinrich Fritsch a highly regarded surgeon and teacher at the University in Bonn described the first case of intra uterine adhesions. (he trained Hermann Johannes Pfannenstiel). In 1927, Bass reported about 20 cases of cervical obstruction in 1500 patients who had undergone induced abortions in a Russian Hospital after the legalislation of abortions in Russia. Stamer decribed another 24 cases in Copenhagen in 1946. Joseph G. Asherman a Czech immigrant from Israel described in 1948 the frequency, etiology, and symptoms, of intrauterine adhesions. Since then Asherman syndrome has been used to describe the disease. Fritsch H. Ein Fall von volligen Schwund der Gebaumutterhohle nach Auskratzung. Zentralbl Gynaekol 1894;18:1337–42. Bass B. Ueber die Verwachsungen in der cervix uteri nach curettagen. Zentralbl Gynakol 1927;51:223. Stamer S. Partial and total atresia of the uterus after excochleation. Acta Obstet Gynecol Scand 1946;26:263–97. Asherman JG. Amenorrhoea traumatica (atretica). J Obstet Gynaecol Br Emp 1948;55:23–30. Asherman JG. Traumatic intrauterine adhesions. J Obstet Gynaecol Br Emp 1950;57:892–6. Asherman JG. Traumatic intrauterine adhesions and their effects on fertility. Int J Fertil 1957;2:49–54. VVOG 2014 Mark Hans Emanuel m@emanuel.nl

VVOG 2014 Mark Hans Emanuel m@emanuel.nl Definition 2 criteria intra-uterine adhesions due to trauma of the endometrium of gravid or non gravid uterus presence of symptoms From Asherman’s original definition, the syndrome was a consequence of trauma to the endometrium caused by curettage of the gravid uterus. In our opinion, the diagnosis of Asherman syndrome should be based on 2 criteria. Furthermore we believe that Asherman is important to differentiate from intentional intrauterine adhesions for example adhesions after endometrium abblation VVOG 2014 Mark Hans Emanuel m@emanuel.nl

What do we know about Asherman Syndrome? rare highest level hysteroscopic surgery no RCT’s high outcome variation VVOG 2014 Mark Hans Emanuel m@emanuel.nl

What do we know about Asherman Syndrome? rare highest level hysteroscopic surgery no RCT’s high outcome variation VVOG 2014 Mark Hans Emanuel m@emanuel.nl

What do we know about Asherman Syndrome? rare? highest level hysteroscopic surgery no RCT’s high outcome variation VVOG 2014 Mark Hans Emanuel m@emanuel.nl

Centralized Care in The Netherlands small geographical area small language area only 1000 gynecologists 16.8 mio citizens social media /chat sites VVOG 2014 Mark Hans Emanuel m@emanuel.nl

VVOG 2014 Mark Hans Emanuel m@emanuel.nl baseline n % Symptoms Menstrual abnormalities 537 84.2 Subfertility 44 6.9 Both 42 6.6 Menstrual pattern   Amenorrhea 413 64.7 Hypomenorrhea 190 29.8 Eumenorrhea 35 5.5 Retrospective Cohort 2003-2013 total 638 patients mean age 35 years The majority of patients had menstrual abnormalities and suffered from amenorrhea or hypomenorrhea VVOG 2014 Mark Hans Emanuel m@emanuel.nl

VVOG 2014 Mark Hans Emanuel m@emanuel.nl causal procedures % First Trimester procedures 56.9 Caesarean section 2.9 Post partum procedures 37.0 No causal procedure (genital TB) 0.6 Of all patients in 95,8% Asherman disease was preceded by a pregnancy related intra uterine operative procedure. More than half of all cases this was a first trimester curettage due to a miscarriage VVOG 2014 Mark Hans Emanuel m@emanuel.nl

research, treatment and expertise Treatment Protocol Hysteroscopy with Fluoroscopic Control IUD & Hormonal Medication 6 weeks Second Look Hysteroscopy 2 months There is a long time of experience in our center of approximately 25 years, with a high volume of cases, approximately 5 per week. We estimate that we operate 60% of all Asherman patients in The Netherlands. This is feasible due to fact that the we are such a small country, with relatively small travel distances and a high population rate and therefore centralization of problematic cases is common. Asherman Expertise Centre research, treatment and expertise VVOG 2014 Mark Hans Emanuel m@emanuel.nl

Hysteroscopy with Fluoroscopic Control Wamsteker, de Blok and Emanuel used since 1990 described in 1997 Broome and Vancaillie 1999 In the last 25 years at least 1500 cases were operated with a combination of operative hysteroscopy with conventional instruments and intra operative fluoroscopy. In this way we are able to identify ‘blocked’ areas of endometrium in the uterine cavity behind or above adhaesions. In this way we can also see otherwise blind-ending parts of open cavity. One of the benefits of this technique is the early detection of a false route or perforation and that tubal patency can be assessed during the procedure, as the landmark of a proper anatomical restoration of the uterine cavity. With the use of a small 3mm optic and a 4.5-6,5mm continuous sheath, visualization can be assured and blind dilation is prevented throughout the whole procedure. Broome JD, Vancaillie TG. Fluoroscopically guided hysteroscopic division of adhesions in severe Asherman syndrome. Obstet Gynecol 1999;93:1041–3. VVOG 2014 Mark Hans Emanuel m@emanuel.nl

VVOG 2014 Mark Hans Emanuel m@emanuel.nl

Grade of Intra Uterine Adhesions ESGE Internal cervical os 2 Internal cervical os 2a 3 Uterine cavity For whom is not familiar with this classification, here an overvieuw Uterine cavity 4 Uterine cavity 5 VVOG 2014 Mark Hans Emanuel m@emanuel.nl

VVOG 2014 Mark Hans Emanuel m@emanuel.nl grade n 1st attempt % success 2nd 3rd 1 25 100 2 27 2a 218 99.1 3 201 80.6 95.5 4 106 60.4 94,3 97.1 5 50 16.0 44.0 60.0 More than one procedure was offered to our patients when restoration of the uterine cavity was not successful. We classified surgery succes full if all three of the following criteria were met: a normalised uterine cavity free of adhesions with hysteroscopic visualization of both tube ostia No adhesions at the hysteroscopic 2 months control visit after surgery Normal menstrual blood flow. Katz Z, Ben-Arie A, Lurie S, Manor M, Insler V. Reproductive outcome following hysteroscopic adhesiolysis in Asherman’s syndrome. Int J Fertil Menopausal Stud 1996;41:462–5. Thomson AJ, Abbott JA, Kingston A, Lenart M, Vancaillie TG. Fluoroscopically guided synechiolysis for patients with Asherman’s syndrome: menstrual and fertility outcomes Fertil Steril. 2007 Feb;87(2):405-10   VVOG 2014 Mark Hans Emanuel m@emanuel.nl

VVOG 2014 Mark Hans Emanuel m@emanuel.nl grade n 1st attempt % success 2nd 3rd 1 25 100 2 27 2a 218 99.1 3 201 80.6 95.5 4 106 60.4 94,3 97.1 5 50 16.0 44.0 60.0 More than one procedure was offered to our patients when restoration of the uterine cavity was not successful. We classified surgery succes full if all three of the following criteria were met: a normalised uterine cavity free of adhesions with hysteroscopic visualization of both tube ostia No adhesions at the hysteroscopic 2 months control visit after surgery Normal menstrual blood flow. Katz Z, Ben-Arie A, Lurie S, Manor M, Insler V. Reproductive outcome following hysteroscopic adhesiolysis in Asherman’s syndrome. Int J Fertil Menopausal Stud 1996;41:462–5. Thomson AJ, Abbott JA, Kingston A, Lenart M, Vancaillie TG. Fluoroscopically guided synechiolysis for patients with Asherman’s syndrome: menstrual and fertility outcomes Fertil Steril. 2007 Feb;87(2):405-10   total in 1 to 3 attempts n % Complete 594 94.7 Incomplete 7 1.1 Drop-out 26 4.1

VVOG 2014 Mark Hans Emanuel m@emanuel.nl Yu et.al. Fertil Steril 2008 More than one procedure was offered to our patients when restoration of the uterine cavity was not successful. We classified surgery succes full if all three of the following criteria were met: a normalised uterine cavity free of adhesions with hysteroscopic visualization of both tube ostia No adhesions at the hysteroscopic 2 months control visit after surgery Normal menstrual blood flow. Katz Z, Ben-Arie A, Lurie S, Manor M, Insler V. Reproductive outcome following hysteroscopic adhesiolysis in Asherman’s syndrome. Int J Fertil Menopausal Stud 1996;41:462–5. Thomson AJ, Abbott JA, Kingston A, Lenart M, Vancaillie TG. Fluoroscopically guided synechiolysis for patients with Asherman’s syndrome: menstrual and fertility outcomes Fertil Steril. 2007 Feb;87(2):405-10   Total in 1 to 3 attempts No. % Complete 594 94.7 Incomplete 7 1.1 Drop-out 26 4.1

VVOG 2014 Mark Hans Emanuel m@emanuel.nl 627 incomplete 125 (19.9%) 112 incomplete 33 (5.2%) 20 incomplete 7(1.1%) drop-out 13 (2.1%) drop-out 13 (2.1%) VVOG 2014 Mark Hans Emanuel m@emanuel.nl

Spontaneous Recurrence of Adhesions grade n adhesion recurrence % 1 5/25 20.0 2 5/27 18.5 2a 39/217 18.0 3 41/201 20.4 4 32/104 30.8 5 7/28 25.0 total 129/602 21.4 Patients with Asherman syndrome were defined as having recurrent adhesions, if they had a successful surgery and normal control hysteroscopy, but spontaneous adhesions were observed during a new hysteroscopy Overall 21.4% recurrence rate These recurrence rates are smaller then compared to international literature VVOG 2014 Mark Hans Emanuel m@emanuel.nl

Spontaneous Recurrence of Adhesions Patients with Asherman syndrome were defined as having recurrent adhesions, if they had a successful surgery and normal control hysteroscopy, but spontaneous adhesions were observed during a new hysteroscopy Overall 21.4% recurrence rate These recurrence rates are smaller then compared to international literature Yu et.al. Fertil Steril 2008 VVOG 2014 Mark Hans Emanuel m@emanuel.nl

VVOG 2014 Mark Hans Emanuel m@emanuel.nl Primary Prevention 1st trimester post-partum Patients with a miscarriage in their medical history had a better chance of a successful surgery than patients with post partum problems. Post partum procedures are more prone to give severe adhesions and therefore diminish the chance of a successful surgery We advocate that post partum remnants procedures should be carefully approached and if possible hysteroscopic techniques should be used in order to minimalize damaging the uterus in stead of blind curettages. In our data set most patients only had one curettage in their medical history (66.9%). Patients with more than one miscarriage curettage in their medical history in our data set had less severe adhesions. This might imply that the individual constitutional element of the endometrium is more responsible for developing Asherman syndrome after intra uterine surgery than the procedure in itself or the technique that was used in the preceding intra-uterine procedures. The problem is that the number needed to treat in primary prevention is to high because of the rareness of the disease VVOG 2014 Mark Hans Emanuel m@emanuel.nl

Recommendations for Future Research VVOG 2014 Mark Hans Emanuel m@emanuel.nl

Secondary Prevention RCT’s SEPA I Adjunctive Hormones vs. None SEPA II IUD vs. Foley/Cook catheter vs. Hyalobarrier We strongly advocate centralization of Asherman surgery to reach higher volumes. Especially since randomized clinical are lacking in this field mainly due to the fact that recruiting patients for inclusion is difficult because of the small numbers of individual centers. By centralizing the care for Asherman patients this could be accomplished easier. In the ACOG Bulletin of 2010, 2 suggestions were made for future research This is the exact 2 studies that we currently are running in the Asherman Expertice Centre SEPA1 Secondary Prevention of Morbus Asherman Evaluation of endometrium stimulation with estrogen gestagen post hysteroscopic adhesiolysis SEPA2 Evaluation of placement of a triangular uterine balloon catheter and placement of a cupper intrauterine device (Cu-IUD) to maintain separation of the cavity and mechanically to prevent early and late recurrence of adhesions VVOG 2014 Mark Hans Emanuel m@emanuel.nl

Life time Follow up Database I-follow up study database approximately 1500 patients starting 1989 Patients already know that they never get rid of us The ultimate outcome of a successful adhesiolysis should be life birth after surgery. We are currently investigating all patients who had surgery in our referral institution and completing the numbers and outcome on pregnancies and deliveries by a systematic large follow-up investigation that was approved by the local Institutional Review Board. We will report the results of this evaluation in the near future. VVOG 2014 Mark Hans Emanuel m@emanuel.nl

VVOG 2014 Mark Hans Emanuel m@emanuel.nl Take to Work Messages Best Treatment in our hands Hysteroscopy with Fluoroscopic Control Centralization for achieving higher Success Rates Primary Prevention should be focused on Post- partum Procedures Need for EBM treatment for Secondary Prevention VVOG 2014 Mark Hans Emanuel m@emanuel.nl

VVOG 2014 Mark Hans Emanuel m@emanuel.nl Follow us Thank you for your attention http://www.asherman.nl VVOG 2014 Mark Hans Emanuel m@emanuel.nl

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