Infertility, Pregnancy
Conditions
Keywords
Endometrial Biopsy, Endometrial Sampling, In Vitro Fertilization, Pregnancy, Implantation
Brief summary
Animal and clinical studies have suggested that local tissue trauma can promote the process of an embryo implanting in the uterine cavity. The clinical studies have been performed in patients with a history of previously failed treatments using in vitro fertilization; a process of stimulating many eggs from a women and removing them from the body, to allow fertilisation with sperm to occur in a laboratory setting. The embryos are then replaced into the uterine cavity. This study questions whether endometrial biopsy (placing a small straw like catheter through the cervix and into the uterine cavity to take a sample of tissue via suction into the bore of the catheter), within 5-10 days of starting a cycle of in vitro fertilization, will improve pregnancy outcome for patients in the first or second cycle of treatment. The hypothesis is that endometrial biopsy will improve pregnancy outcome. The study is a randomized multicentre study involving 3 Canadian fertility centres.
Detailed description
Although the data are preliminary, there are studies suggesting that mild endometrial trauma in the cycle preceding IVF increases pregnancy rates, at least in women with recurrent implantation failure. Whether endometrial biopsy could promote implantation and improve pregnancy rates in the larger population of women undergoing IVF has yet to be explored. The present study will address this question and examine the impact of endometrial biopsies on IVF outcomes in the context of a randomized controlled trial. The optimal timing of the endometrial biopsy in the cycle preceding IVF has not been determined, but the majority of the studies have included a biopsy in the mid-luteal phase of the preceding cycle. In order to allow an adjuvant therapy to IVF that would be considered tolerable to a subject, and applicable to a large infertile women population, it was determined that a single endometrial biopsy, performed approximately 1 week prior to the start of controlled ovarian hyperstimulation (COH) in an IVF cycle, would be the simplest, most flexible, and generalizable intervention to study its effects on pregnancy rates. All other components of the IVF treatment will remain constant with approximately 8-12 days of ovarian stimulation, human chorionic gonadotrophin (HCG) trigger being administered in that time frame and oocyte retrieval occuring 36 hours later from trigger. The embryo transfer will take place either day 3 or day 5 after oocyte retrieval.
Interventions
DEVICEEndometrial Biopsy
An endometrial biopsy is performed using a sampling device known as a pipelle catheter which is introduced into the uterine cavity. The inner core is withdrawn creating suctional pressure into the hollow bore of the cavity, which allows acquisition of endometrial tissue upon rotation in the cavity. This is removed and the tissue sent for pathologic examination.
Sponsors
Jon Havelock
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
Women undergoing first or second IVF cycle, with or without ICSI * Age 18-39 * BMI 18-35 kg/m2 * Uterine cavity evaluation (hysterosalpingogram, sonohysterogram, hysteroscopy) in the preceding 24 months * Early follicular phase (Day 2 or Day 3) serum FSH, evaluated in the preceding 6 months ONE of the following: * Non- oral contraceptive pill (non-OCP) subjects: Documented LH surge 9-11 days prior to enrollment * Current OCP subjects: OCP use for ≥ 10 days * Use of long GnRH agonist or GnRH antagonist protocol * Subject able to give informed consent
Exclusion criteria
* Prior enrolment in this study * Any prior early follicular phase serum FSH level ≥12 IU/L * Previous poor ovarian response, defined as prior IVF cycle cancelled for poor response, or ≤4 oocytes retrieved * IVF for pre-implantation genetic diagnosis (PGD) or fertility preservation * Diabetes mellitus or uncontrolled thyroid disease * Abnormal uterine cavity, such as unresected submucosal fibroids, uterine septum, Mullerian anomaly such as bicornuate or unicornuate uterus or intrauterine adhesions * Hydrosalpinx that has not been removed or surgically ligated * Any contraindication to endometrial biopsy * Office hysteroscopy or other uterine procedure planned or performed during cycle preceding IVF stimulation * Use of surgically retrieved sperm
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Pregnancy Rate | Five weeks gestation, as dated from the egg retrieval | Clinical pregnancy rate, defined as transvaginal ultrasound documentation of fetal heartbeat at five weeks gestation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Live Birth Delivery Rate | Within twelve months of the cycle start date | Live birth delivery rate will be the number of live birth deliveries expressed per 100 initiated cycles, aspiration cycles or embryo transfer cycles, for which the denominator (initiated, aspirated or embryo transfer cycles) will be specified. Live birth delivery will include deliveries that resulted in at least one live birth. The delivery of a singleton, twin or other multiple births will be registered as one delivery. |
| Fertilization Rate | 24 hours after egg retrieval | Fertilization rate will be the number of zygotes resulting from insemination by IVF or injection by intracytoplasmic sperm injection, expressed as a ratio to the total number of oocytes inseminated or injected. |
| Normal Fertilization Rate | 24 Hours from egg retrieval | Normal fertilization rate will be the number of normal zygotes resulting from insemination by IVF or injection by ICSI, expressed as a ratio to the total number of oocytes inseminated or injected. |
| Implantation Rate | Five weeks gestation, as dated from the egg retrieval | The number of gestational sacs seen at ultrasound, divided by the total number of embryos transferred |
| Endometrial Pattern | Day of administration of human chorionic gonadotropin (8-12 days into ovarian stimulation) | The endometrial pattern will be categorised as either trilaminar (triple stipe pattern) or hyperechoic (diffusely echogenic)at the time of transvaginal ultrasound assessment. |
| Percentage of subjects with embryos cryopreserved | At the latest, day 6 after egg retrieval | Total number of participants with embryos in excess, that met criteria for cryopreservation |
| The number of embryos cryopreserved per subject | At the latest, day 6 after egg retrieval | The number of embryos each individual participant had in excess, meeting criteria for cryopreservation |
| Endometrial Thickness | Day of administration of human chorionic gonadotropin (8-12 days into ovarian stimulation) | As assessed by transvaginal ultrasound, the maximum dimension of the endometrial cavity echo in an antero-posterior plane. |
Countries
Canada
Outcome results
None listed