PREVENTION OF MULTIPLES FROM A CLINICIAN’S STANDPOINT Bulent Urman M.D. American Hospital of Istanbul

TRENDS IN EMBRYO TRANSFER PRACTICE NO LEGAL OR ETHICAL RESTRICTIONS IN THE NUMBER OF TRANSFERRED EMBRYOS FROM SINGLE TO MULTIPLE EMBRYO TRANSFERS PREVENTION OF TRIPLETS AND HOMP PREVENTION OF TWINS EARLY 1980s TODAY PREGNANCY========HEALTHY BABIES========HEALTHY SINGLE BABY

Current Turkish Legislation A maximum of 3 embryos are allowed to be transferred The number can be increased if the clinician feels that it is indicated under special circumstances

How many embryos do we actually transfer?

Is there a need to change the current policy? Should we decrease the number of transferred embryos?

If yes: Questions! Why should we reduce the number of transferred embryos? How is the success of ART affected? SET vs DET Are we ready to do it in Turkey? A proposed national model

Factors affecting embryo transfer policy Pressure to be successful Insurance non coverage Pressure form patients-twins are the ideal outcome Implantation rates of the individual center Cryopreservation –Availability –Uptake

From Blennborn et al. Hum Reprod 2005 The couple’s decision-making in IVF: one or two embryos at transfer?

Probabilities for singleton and multiple pregnancies after in vitro fertilization Peter M. Martin, M.D.,*† and H. Gilbert Welch M.D., M.P.H.†‡ FERTILITY AND STERILITYt VOL. 70, NO. 3, SEPTEMBER 1998

Probabilities for singleton and multiple pregnancies after in vitro fertilization Peter M. Martin, M.D.,*† and H. Gilbert Welch M.D., M.P.H.†‡ FERTILITY AND STERILITYt VOL. 70, NO. 3, SEPTEMBER 1998

Probabilities for singleton and multiple pregnancies after in vitro fertilization Peter M. Martin, M.D.,*† and H. Gilbert Welch M.D., M.P.H.†‡ FERTILITY AND STERILITYt VOL. 70, NO. 3, SEPTEMBER 1998

Probabilities for singleton and multiple pregnancies after in vitro fertilization Peter M. Martin, M.D.,*† and H. Gilbert Welch M.D., M.P.H.†‡ FERTILITY AND STERILITYt VOL. 70, NO. 3, SEPTEMBER 1998

Pregnancy and live birth rates after the transfer of 2-3 embryos Number of embryos transferred No of transfer procedures Number of pregnancies PR/ET %Live birth / transfer % Two from only two available Two from more than two available Three From Brinsden RBM Online 2003

Factors affecting success in IVF Age Tubal infertility Previous IVF outcome Gonadotropin dose –Initial –Total Good quality embryos –Available –Transferred –Cryopreserved From Strandell et al. 2000

Is there a subset of couples who would benefit from (no compromise in PR and no twins) from single embryo transfer?

Pregnancy rate according to the number of embryos transferred From Zhang et al. 2008

Multiple pregnancy rate according to the number of embryos transferred From Zhang et al. 2008

From Saldeen and Sundstom Hum Reprod 2005 Results of SET and DET according to embryo morphology

Optimal number of embryos to be transferred based on quality From Hu et al. Fertil Steril 1998

From Roberts et al. Hum Reprod 2009

Cohort studies of SET vs DET StudyCyclesSingle ETDouble ET PR %Twins %PR %Twins % Gerris / De Sutter / Tiitinen / Catt / Gerris Martikainen / NA TOTAL From Gerris et al. Hum Reprod Update 2005

Prospective evaluation of elective single-embryo transfer versus double-embryo transfer following in vitro fertilization: a two-year French hospital experience From Leniaud et al. Gynecol Obstet Fertil Feb;36(2):159-65

Randomized trials of SET vs DET StudyCyclesSingle ETDouble ET PR %Twins %PR %Twins % Gerris Martikainen Gardner Thurin TOTAL From Gerris et al. Hum Reprod Update 2005

From Fiddelers et al. Hum Reprod 2006 Single versus double embryo transfer: cost-effectiveness analysis alongside a randomized clinical trial

In unselected patients, elective single embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared with double embryo transfer: a randomized controlled trial From van Monfoort et al. Hum Reprod 2006

Better embryo selection? Blastocyst transfer PGS

Single vs double blastocyst transfer: randomized trial

Papanikolaou, E. et al. N Engl J Med 2006;354:

A prospective randomized controlled trial of preimplantation genetic screening in the "good prognosis" patient From Meyer et al. Fertil Steril 2008

Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis From Kjellberg et al. Hum Reprod 2006

Transfer policy in the American Hospital Prior to August 2000 –Up to 3-4 embryos until the age of 39 –5-6 embryos after 40 After August 2000 –Maximum 2 good quality fresh or frozen thawed embryos up to 37 If embryo quality is suboptimal 3 is allowed –Maximum 3 good quality fresh or frozen thawed embryos after 37 If embryo quality is suboptimal 4 is allowed after 40

Transfer edilen ortalama embryo sayısı

7300 D3 embryo transferinde klinik gebelik oranları

1100 D5 embryo transferinde klinik gebelik oranları

Incidence of singletons, twins, and HOMPs in the American Hospital

Number of embryos transferred in view of Efficacy –Implantation and pregnancy rates Side effects –Multiple pregnancies Cost effectiveness –Society resources –Can the system handle increasing multiples?

< ve üzeri İyi prognozlu Normal prognozlu Kötü prognozlu TRANSFER EDİLEBİLİR EMBRYO SAYISI İLE İLGİLİ TÜRKİYE MODELİ ÖNERİSİ

İyi prognoz kriterleri İyi yanıt veren kadında ilk ART siklusu Kryoprezervasyon için uygun olan embryoların varlığında selektif embryo transferi yapma olasılığı Doğum ile sonuçlanan ART gebeliği öyküsü 2 veya 3. günde 4 veya 8 hücreli G1 veya G2 embryoların varlığı 5. günde G1 veya G2 blastokistlerin varlığı

Kötü prognoz kriterleri 3. veya sonraki ART siklusları Over stimülasyonuna kötü yanıt (3 veya daha az oositin toplandığı durumlar) Kötü kaliteli embryoların varlığı

Is the Scandinavian model of SET valid in Turkey Pregnancy and implantation rates in Turkish IVF centers are largely unknown In unselected patients, single embryo transfer decreases twin pregnancy rate but also decreases the pregnancy rate Pregnancy rate is dependent on embryo quality, women's age, rank of IVF attempt and also other variables That is the reason why a flexible policy of transfer adapted to each couple is preferable Each couple and each IVF team must keep the freedom to choose how many embryos must be transferred to obtain healthy babies, and to avoid twin pregnancies

CONCLUSIONS Q: Should we prevent multiples? A: Yes Q: Should we decrease the number of embryos we transfer? A: Yes Q: Is IVF the only problem? A: No

Conclusions Infertile couples with good prognosis should be encouraged to wait Life style changes improving fertility should be promoted IUI should be considered in the natural cycle. If COH is instituted nor more than 2 follicles should be the aim Mild stimulation protocols for IVF should be adopted Elective SET should be considered in good prognosis couples Transfer policy according to prognostic factors should be adopted

Ülkelerde IVF merkezi başına düşen nüfus (x 1000)

IVF VE TURKİYE Sektörel sorunlar Etik sorunlar Standardizasyon Denetim Yönetmelikler Başarı Çoğul gebelikler Veri toplama

SB VE SGK SORUNLARIMIZA HASSASİYET GÖSTERİYOR MU?

TSRM SURVEY ON MULTIPLES AND DATA COLLECTION

Increasing multiple pregnancies in IVF is an important health issue in Turkey

Twin pregnancies significantly increase maternal and fetal morbidity and mortality

The allowed number of 3 embryos that can be transferred according to the current legislation is reasonable

Decreasing the number of embryos to be transferred from 3 to 2 will prevent triplets without significantly affecting overall pregnancy rates

Elective single embryo transfer is an acceptable option in good prognosis couples

Single embryo transfer should be mandatory for all couples undergoing their first and second IVF cycle

The number of embryos that is allowed for transfer should be variable according to the prognostic factors

Decreasing the number of embryos to be transferred from 3 to 2 will prevent triplets without significantly affecting overall pregnancy rates

< ve üzeri İyi prognozlu Normal prognozlu Kötü prognozlu TRANSFER EDİLEBİLİR EMBRYO SAYISI İLE İLGİLİ TÜRKİYE MODELİ ÖNERİSİ

The model proposed by the TSRM is logical for our country

Who should collect the data?

How should the data be collected