LUTEAL PHASE SUPPORT FOR ICSI PATIENTS

Professor Salah Abd Rabbo Reproductive biology and infertility

WHEN EDWARDS AND STEPTOE STARTED CLINICAL IVF, HUMAN OOCYTES WERE SUCCESSFULLY FERTILIZED AND GROWN IN VITRO, HOWEVER, NO PREGNANCY RESULTED FOR THE FIRST SEVEN YEARS.

IT WAS THEN REALIZED THAT THE FAILURE OF EMBRYOS TO IMPLANT WAS DUE TO LUTEAL PHASE DISRUPTION

)ROBERT AND EDWARDS 2001)

THE ASPIRATION OF GRANULOSA CELLS THAT SURROUND THE OOCYTE, AND THE USE OF GnRh a DURING A R T CAN INTERFERE WITH THE PRODUCTION OF PROGESTERONE DURING THE LUTEAL PHASE WHICH IS NECESSARY FOR IMPLANTATION
( GARCIA ET AL. FERTIL&STERIL 1981 )

 LUTEAL

PHASE SUPPORT IN IVF AGONIST AND ANTAGONIST PROTOCOLS IS CONSIDERED ESSENTIAL FOR OPTIMAL SUCCESS
HABAYTER,MUASHER FERTIL.STERIL 2008 APRIL (4) 749-58

ALL SYSTEMIC REVIEWS AND METAANALYSIS HAVE CONFIRMED THE IMPORTANCE OF LPS IN ART

PRITTS ET AL. HUMAN REPRODUCTION 2002 DAYA ET AL. COCHRANE DATA BASE SYS REV 2004

LUTEAL PHASE SUPPORT LPS

Which support ?

WHEN WE START? DAY OF INITIATION

WHAT IS THE DOSE?

WHAT IS THE ROUTE OF ADMINISTRATION

WHAT IS THE DURATION

DIFFERENT REGIMENS ARE USED

Which support ?

PROGESTERON

PROGESTERON AND ESTROGEN

)GnRh-a )

( HCG (

PROGESTERONE
PROGESTERONE ADMINISTRATION SIGNIFICANTLY IMPROVED FERTILITY OUTCOMES IN ART COMPARED TO NO TREATMENT.

SOLIMAN ET AL. FERTIL& STERIL 1994

HCG
HCG IS EQUIVALENT TO PROGESTERONE BUT HAS HIGHER OHSS

PENZIAS FETIL& STERIL 2002

Luteal E 2 supplementation
Higher preg and implantation rates are observed in icsi cycles in women supplemented with E2 in the luteal phase

Drakakis et al, Gynecol,Endocrinol 2007

Luteal E 2 supplementation

Estrogen is required to stimulate P receptors replenishment in the endometrium , so P can act

L P ESTROGEN

Oral 2-6 mg/day Gelbaya et al, Fertil,steril 2008 Transdermal Serna et al fertil,steril 2008 And vaginal Fertil,steril 2008 89 (3) 554-61 Did not change ICSI outcome

Luteal phase E 2 level

luteal E2 conc seems to be a promising marker of successful clinical pregnancy

Ganesh et al, fertil,steril mar 2008,

GnRh-a
Implantation rates are less in antagonist cycles
(Al-Inany et al. cochrane data base 2006)

But if antagonist frozen embryos used in natural cycles implantation improves

(Zikopoulos et al. Fertil&steril 2004)

GnRh-a
GnRH receptors in endometrium are blocked after GnRH antagonist ( Meserman et et al. Human Reproduction 2003( Luteal phase administration of GnRH-a has a beneficial effect on implantation in LP
(tesarike et al. Human Reproduction 2006)

GnRH-a
IT IS USED AT TIME OF HCG
(Schachter et al Fertil&Steril 2008)

OR DURING THE LUTEAL PHASE

(et al. Hum Tesarik Reprod 2006)

WHEN WE START? DAY OF INITIATION

ROUTE OF PROGESTERONE SUPPLEMENTATION

ROUTE
IN 1992 SMITZ ET AL. REPORTED THAT THE IM ROUTE IS THE MOST COMMONLY USED

HUMAN REPRODUCTION 1992

ROUTE
ORAL PROGESTERONE WAS FOUND TO BE ASSOCIATED WITH SIGNIFICANTLY LOWER IMPLANTATION AND PREGNANCY RATES, HIGH MISCARRIAGE RATES,OR BOTH COMPARED WITH IM OR VAGINAL ROUTE
FRIEDLER ET AL. HUMAN REPRODUCTION 1999

ROUTE
Compared to vaginal gel ,IM injections have significantly higher pregnancy And delivery rates.

Guesa et al.ESHRE 2001

ROUTE
LOCAL AND SYSTEMIC ALLERGIC REACTIONS TO THE OIL IN IM INJECTIONS MAY RESULT.

PENZIAS AND ALPER REPROD BIOMED ONLINE 2003

WHAT IS THE DOSE?

DOSE
THE DOSE OF IM PROGESTERONE IS 50100mg/day DAILY INJECTION WITH 25 AND 100 mg PROGESTERONE WAS COMPARED, AND NO SIGNIFICANT DIFFERENCE IN CLINICAL PREGNANCY OR DELIVERY RATE WAS FOUND
CHECK ET AL J IN VITRO FERT EMBRYO TRASF 1991

DOSE
ORAL OR VAGINAL PROGESTERONE IS GIVEN IN THE FORM OF MICRONIZED PREPARATION IN A DOSE OF 400-600 mg/day

PRITTS AND ATWOOD HUMAN REPROD 2002

WHAT IS THE DURATION

DURATION
THE DURATION OF LPS IS VARIABLE IN DIFFERENT STUDIES, FROM SUPPLEMENTATION FOR 2 TO 3 WKS ONLY AND THROUGH 10 TO 12 WKS OF GESTATION
PRITTS AND ATWOOD HUMAN REPROD 2002

Duration of LPS
In a prospective R study comparing LPS for ICSI patients up to the first US compared with an additional three weeks,done in 21 IVF centers.

Aboulghar et al. Human Reproduction 2008

Duration of LPS
The study found no statistical difference reguarding miscarriage rate up to 20 wks. They concluded that their randomized trial did not support extending LPS beyond the day of first us demonstrating pulsations
Aboulghar et al. Human Reproduction 2008

CONCLUSIONS

SUMMARY

LPS IS ESSENTIAL FOR ICSI PATIENTS

PROGESTERONE IS THE MOSTLY USED

HCG IS ASSOCIATED WITH HIGHER OHSS

ADDITION OF ESTROGEN TO PROGESTERONE MAY IMPROVE IMPLANTATION RATE MIDLUTEAL E2 DEFINES PATIENTS IN NEED FOR E2 SUPPLEMENTATION

GNRH-a AT TIME OF HCG IMPROVES PREG RATE IN ANTAGONIST PROTOCOL

IM, AND VAGINAL ROUTES ARE THE MOSTLY PREFERRED THE INITIATION, THE DOSE AND THE DURATION OF LPS ARE STILL GREATLY VARIABLE, NEED FURTHER STUDIES.