Ignite Creation Date:
2024-05-06 @ 12:23 AM
Last Modification Date:
2024-10-26 @ 10:49 AM
Study NCT ID:
NCT01565265
Status:
COMPLETED
Last Update Posted:
2017-05-01
First Post:
2012-02-28
Brief Title:
Comparing Ovarian Stimulation for Assisted Reproduction With Two Different Forms of Pituitary Suppression
Sponsor:
University Hospital Basel Switzerland
Organization:
University Hospital Basel Switzerland
Study Overview
Official Title:
Prospective Randomized Study Comparing Ovarian Stimulation With Pergoveris Supported by a GnRH Agonist in a Long Protocol Versus Multidose GnRH Antagonist Regimen in Young Infertile Women Treated With ICS
Status:
COMPLETED
Status Verified Date:
2017-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Pergoveris
Brief Summary:
The purpose of this study is to assess the non-inferiority of a multidose GnRH antagonist cetrorelix regimen to a GnRH agonist triptorelin long protocol in young infertile women undergoing ovarian stimulation with Pergoveris 150 IU75 IU r-hFSH r-hLH for ICSI treatment because of male infertility
To assess the efficacy of ovarian stimulation using either a GnRH antagonist cetrorelix or a GnRH agonist triptorelin long protocol in infertile women with good prognosis and to determine the safety of ovarian stimulation
Subsample analysis in 10 patients of each of both arms serum samples will be collected daily during the stimulation period and be stored frozen at -70 C The following hormone concentrations will be measured later in single assay batches LH FSH oestradiol progesterone androstenedione testosterone inhibin A inhibin B AMH
Multinational multicentre open label randomized 2-arm parallel-group phase IV study Eligible patients will be randomly allocated to one of the two groups the agonist group will receive Decapeptyl 01 mg triptorelin starting in the mid-luteal phase of the natural cycle until downregulation until the day of ovulation induction The antagonist group will receive cetrorelix 025 mg from stimulation day 6 to ovulation induction In both groups Pergoveris 150 IU75 IU r-hFSHr-hLH will be used for ovarian stimulation from cycle day 2 to ovulation induction
To assess the efficacy of ovarian stimulation using either a GnRH antagonist cetrorelix or a GnRH agonist triptorelin long protocol in infertile women with good prognosis and to determine the safety of ovarian stimulation
Subsample analysis in 10 patients of each of both arms serum samples will be collected daily during the stimulation period and be stored frozen at -70 C The following hormone concentrations will be measured later in single assay batches LH FSH oestradiol progesterone androstenedione testosterone inhibin A inhibin B AMH
Multinational multicentre open label randomized 2-arm parallel-group phase IV study Eligible patients will be randomly allocated to one of the two groups the agonist group will receive Decapeptyl 01 mg triptorelin starting in the mid-luteal phase of the natural cycle until downregulation until the day of ovulation induction The antagonist group will receive cetrorelix 025 mg from stimulation day 6 to ovulation induction In both groups Pergoveris 150 IU75 IU r-hFSHr-hLH will be used for ovarian stimulation from cycle day 2 to ovulation induction
Detailed Description:
In assisted reproductive technology ART follicular growth is stimulated with exogenous gonadotropins to obtain multiple mature oocytes for fertilization In a natural cycle oocyte maturation and ovulation is triggered by endogenous luteinizing hormone LH To prevent a premature surge of LH and subsequent premature ovulation and cancellation of the ART cycle a gonadotropin releasing hormone GnRH agonist is commonly used to inhibit endogenous gonadotropin release leading to premature ovulation or luteinization After a short-term initial stimulation of the pituitary gland continuous administration of a GnRH agonist leads to the downregulation of GnRH receptors of the pituitary and thus prevents synthesis and release of follicle-stimulating hormone FSH and LH from that organ
Endogenous gonadotropin release may also be prevented by using GnRH antagonists instead of GnRH agonists During the past decade two GnRH antagonists cetrorelix ganirelix have been licensed for prevention of premature LH surge and ovulation during ovarian hyperstimulation for assisted reproduction The antagonist competes directly with the physiological GnRH for binding to the pituitary GnRH receptors and provides quicker suppression of gonadotropin release without the initial flare up Compared with the GnRH agonist long protocol GnRH antagonists require a considerably shorter treatment period less exogenous gonadotropin for ovarian stimulation and are associated with fewer side effects and a lower risk of ovarian hyperstimulation syndrome OHSS An early meta-analysis from 2002 which included the first studies comparing GnRH agonist and antagonist treatment regimens showed that clinical pregnancy was lower with GnRH antagonist treatment However there were no statistically significant differences in life-birth rate or in the probability of life birth between the protocols as shown in a more recent review However GnRH agonists are still routinely used in most infertility centres whereas GnRH antagonists are still preferentially prescribed to older women with unfavourable prognosis The equivalence of both protocols has only been evaluated in ovarian hyperstimulation based on recombinant FSH only
Another difference among both protocols consists of the sudden blockage of endogenous LH secretion caused by the administration of the GnRH antagonist which is usually given when the follicles reach the size of 12 mm around day 6 of the menstrual cycle At that developmental stage the LH receptor is present in the follicles participating in follicular function In women treated with the long protocol low endogenous levels of LH have been associated with low pregnancy rates At present conflicting data have been reported with regard to the effect of either low or high levels of LH during the midfollicular phase on the pregnancy rates regardless whether GnRH agonists or GnRH antagonists were used However all these studies were performed with recombinant FSH lacking all LH activity and one single day measurement of LH concentration in the serum may not reflect the endocrine activity of LH throughout follicular development The need for the presence of LH during follicular development has been demonstrated unequivocally in women suffering of hypogonadotropic ovarian failure WHO I which lead to the development of Pergoveris 150 IU75 IU
Pergoveris 150 IU75 IU is used to stimulate the development of follicles in the ovaries and was granted European marketing authorization in 2007 It consists of a fixed combination of recombinant human follicle-stimulating hormone r-hFSH and recombinant human luteinizing hormone r-hLH and allows the administration of both substances in a single injection So far no study has been performed to demonstrate the equivalence of Pergoveris in the GnRH antagonist protocol as compared to the long protocol based on a GnRH agonist
The current study aims to assess the non-inferiority of a multidose GnRH antagonist treatment regimen to a GnRH agonist long protocol in young infertile women 36 years with good prognosis undergoing ovarian stimulation with Pergoveris for intracytoplasmic sperm injection ICSI because of non-borderline male infertility In addition the safety of ovarian stimulation with Pergoveris will be evaluated for both treatment regimens especially with regard to the incidence of OHSS
The primary objective of this study is to assess the non-inferiority of a multidose GnRH antagonist cetrorelix regimen to a GnRH agonist triptorelin long protocol in young infertile women undergoing ovarian hyperstimulation with Pergoveris 150 IU75 IU r-hFSH r-hLH for ICSI treatment because of male infertility Non-inferiority is defined by the number of mature metaphase II oocytes available for ICSI
Secondary objectives
To assess the efficacy of ovarian stimulation with Pergoveris using either a GnRH antagonist cetrorelix or a GnRH agonist triptorelin long protocol in infertile women with good prognosis with respect to the number of pregnancies achieved in each group
To determine the safety of ovarian stimulation with respect to the number of women suffering of the ovarian hyperstimulation syndrome OHSS
This is a clinical phase IV multinational multicentre study using an open label randomized 2-arm parallel-group design The study will be conducted at various treatment units in Europe including Switzerland 1 centre and Israel
Eligible patients will be randomly assigned to one of the two treatment arms
agonist group r-hFSHr-hLH 150 IU75 IU Pergoveris daily from cycle day 2 to ovulation induction and triptorelin 01 mg daily from the mid-luteal phase day 21 - 24 of the pre-ART cycle to ovulation induction
antagonist group r-hFSHr-hLH 150 IU75 IU Pergoveris daily from cycle day 2 to ovulation induction and cetrorelix 025 mg daily from cycle day 7 stimulation day 6 to ovulation induction
Endogenous gonadotropin release may also be prevented by using GnRH antagonists instead of GnRH agonists During the past decade two GnRH antagonists cetrorelix ganirelix have been licensed for prevention of premature LH surge and ovulation during ovarian hyperstimulation for assisted reproduction The antagonist competes directly with the physiological GnRH for binding to the pituitary GnRH receptors and provides quicker suppression of gonadotropin release without the initial flare up Compared with the GnRH agonist long protocol GnRH antagonists require a considerably shorter treatment period less exogenous gonadotropin for ovarian stimulation and are associated with fewer side effects and a lower risk of ovarian hyperstimulation syndrome OHSS An early meta-analysis from 2002 which included the first studies comparing GnRH agonist and antagonist treatment regimens showed that clinical pregnancy was lower with GnRH antagonist treatment However there were no statistically significant differences in life-birth rate or in the probability of life birth between the protocols as shown in a more recent review However GnRH agonists are still routinely used in most infertility centres whereas GnRH antagonists are still preferentially prescribed to older women with unfavourable prognosis The equivalence of both protocols has only been evaluated in ovarian hyperstimulation based on recombinant FSH only
Another difference among both protocols consists of the sudden blockage of endogenous LH secretion caused by the administration of the GnRH antagonist which is usually given when the follicles reach the size of 12 mm around day 6 of the menstrual cycle At that developmental stage the LH receptor is present in the follicles participating in follicular function In women treated with the long protocol low endogenous levels of LH have been associated with low pregnancy rates At present conflicting data have been reported with regard to the effect of either low or high levels of LH during the midfollicular phase on the pregnancy rates regardless whether GnRH agonists or GnRH antagonists were used However all these studies were performed with recombinant FSH lacking all LH activity and one single day measurement of LH concentration in the serum may not reflect the endocrine activity of LH throughout follicular development The need for the presence of LH during follicular development has been demonstrated unequivocally in women suffering of hypogonadotropic ovarian failure WHO I which lead to the development of Pergoveris 150 IU75 IU
Pergoveris 150 IU75 IU is used to stimulate the development of follicles in the ovaries and was granted European marketing authorization in 2007 It consists of a fixed combination of recombinant human follicle-stimulating hormone r-hFSH and recombinant human luteinizing hormone r-hLH and allows the administration of both substances in a single injection So far no study has been performed to demonstrate the equivalence of Pergoveris in the GnRH antagonist protocol as compared to the long protocol based on a GnRH agonist
The current study aims to assess the non-inferiority of a multidose GnRH antagonist treatment regimen to a GnRH agonist long protocol in young infertile women 36 years with good prognosis undergoing ovarian stimulation with Pergoveris for intracytoplasmic sperm injection ICSI because of non-borderline male infertility In addition the safety of ovarian stimulation with Pergoveris will be evaluated for both treatment regimens especially with regard to the incidence of OHSS
The primary objective of this study is to assess the non-inferiority of a multidose GnRH antagonist cetrorelix regimen to a GnRH agonist triptorelin long protocol in young infertile women undergoing ovarian hyperstimulation with Pergoveris 150 IU75 IU r-hFSH r-hLH for ICSI treatment because of male infertility Non-inferiority is defined by the number of mature metaphase II oocytes available for ICSI
Secondary objectives
To assess the efficacy of ovarian stimulation with Pergoveris using either a GnRH antagonist cetrorelix or a GnRH agonist triptorelin long protocol in infertile women with good prognosis with respect to the number of pregnancies achieved in each group
To determine the safety of ovarian stimulation with respect to the number of women suffering of the ovarian hyperstimulation syndrome OHSS
This is a clinical phase IV multinational multicentre study using an open label randomized 2-arm parallel-group design The study will be conducted at various treatment units in Europe including Switzerland 1 centre and Israel
Eligible patients will be randomly assigned to one of the two treatment arms
agonist group r-hFSHr-hLH 150 IU75 IU Pergoveris daily from cycle day 2 to ovulation induction and triptorelin 01 mg daily from the mid-luteal phase day 21 - 24 of the pre-ART cycle to ovulation induction
antagonist group r-hFSHr-hLH 150 IU75 IU Pergoveris daily from cycle day 2 to ovulation induction and cetrorelix 025 mg daily from cycle day 7 stimulation day 6 to ovulation induction
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| UBCH001 | OTHER_GRANT | University Hospital of Basel Switzerland | None |