PERFORMING THE EMBRYO TRANSFER: A GUIDELINE PRACTICE COMMITTEE OF ASRM DR. OLUBUNMI LADIPO A Summary presented at The 7th AFRH Conference, Abuja, Nigeria.

Outline Introduction Common Practice Methods Quality of Evidence Strength of Evidence Systematic Review of Literature Recommendations Interventions that are not Beneficial

Introduction Embryo Transfer is one of the most critical steps of IVF. Embryo Transfer pregnancy rates depend on the Clinician performing the transfer. There seems to be no standard protocol for Embryo Transfer procedure. Therefore common practice protocols are examined by systematic review of literatures.

Image Source: Dr Maplani’s Blog Common practice Image Source: Dr Maplani’s Blog

Common practice Step 1: Prepare for embryo transfer procedure by reviewing the prior mock or patient notes. Step 2: Prepare the patient for procedure. Use analgesics and other techniques as needed for patient comfort. Step 3: Identification and matching patient and embryo(s). Step 4: Use TAS for guidance of embryo transfer

Common practice Step 5: Practitioner preparation should include some form of hand washing and sterile latex-free gloves Step 6: Place speculum. Flush or cleanse cervix/vagina with cotton swab or gauze sponge using media or saline Step 7: Remove mucus from endocervical canal. Step 8: Pass transfer catheter

Common practice Step 9: Place the tip of the catheter at the idea location Step 10: Expel the embryo and withdraw catheter immediately Step 11: Check catheter for retained embryo(s); if present, reload in new catheter and re-transfer embryo(s). Step 12: The patient gets up from transfer table and leaves room immediately.

Methods Systematic literature search of relevant articles in electronic data base 2,086 of studies identified and 143 selected for study. Included studies are levels 1 and 2 quality; meta-analysis and relevant articles from the bibliographies of identified articles. Three reviewers; inclusion is by consensus or arbitration.

Quality of evidence Level 1: Evidence obtained from at least one properly designed randomized, controlled trial Level 11-1: Evidence obtained from well designed controlled trials without randomization Level 11-2: Evidence obtained from cohort or case controlled analytical studies, preferably from more than one center or research group

Quality of evidence Level 11-3: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled trials might be regarded as this type of evidence Level 111: Opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees.

Strength of evidence Grade A: There is good evidence to support the recommendation, either for or against Grade B: There is fair evidence to support the recommendation, either for or against. Grade C: There is insufficient evidence to support the recommendation, either for or against.

Patient preparation There is a fair evidence that acupuncture performed around the time of embryo transfer does not improve live birth rates in IVF. (Grade B) There is no sufficient evidence to recommend for or against analgesics to improve IVF-embryo transfer outcomes. (Grade C) There is insufficient evidence to recommend for or against massage therapy to improve IVF-embryo transfer outcomes. (Grade C)

Patient preparation There is insufficient evidence that anesthesia during embryo transfer improves pregnancy rates, given that there are no clear benefits and there are inherent risks associated with anesthesia, routine anesthesia is not recommended to improve IVF-embryo transfer outcomes. (Grade C) There is insufficient evidence to recommend for or against WS- TCM to improve IVF-embryo transfer outcomes. (Grade C)

Patient preparation There is fair evidence based on a single RCT that an antibiotic regimen that includes amoxicillin and clavulanic acid given on the day before and the day of embryo transfer does not improve pregnancy rates, (Grade B). Given this results and lack of other evidence to support prophylatic antibiotics at embryo transfer, a recommendation for routine prophylatic antibiotics cannot be made.

Patient preparation There is fair evidence based on only one RCT that transcutaneous electrical acupoint stimulation (TEAS) improves IVF-embryo transfer outcomes. (Grade B). However, given the lack of any other studies, a recommendation for or against TEAS to improve IVF-ET outcomes cannot be made.

Powdered gloves There is fair evidence based on one, single-center RCT that powdered gloves worn during embryo transfer do not have an adverse effect on pregnancy rates. (Grade B). No specific type of glove is recommended for embryo transfer.

TA ultrasound guidance There is good evidence based on 10 RCTs to recommend TA ultrasound guidance during ET to improve pregnancy and live-birth rates. (Grade A) While selected ultrasound guidance for anticipated difficult embryo transfer may be an alternative to routine ultrasound guidance, there is insufficient evidence to recommend for or against this practice, (Grade C)

Removing Mucus There is fair evidence based on one RCT and one prospective cohort study that there is a benefit to removing cervical mucus at the time of ET to improve clinical pregnancy and live-birth rates. (Grade B)

Type of Catheter There is good evidence to recommend the use of soft ET catheter to improve IVF-ET pregnancy rates. (Grade A). Data on live-birth rates and specific types of soft catheters are limited.

Positioning of catheter There is fair evidence based on six studies (2 RCTs and 4 cohort studies) that embryo transfer catheter placement, affects implantation and pregnancy rates. (Grade B) There is fair evidence based on seven studies (3 RCTs and 4 cohort studies) that placement of the catheter tip in the upper or middle (central) area of the uterine cavity, greater than 1cm from the fundus for embryo expulsion, optimizes pregnancy rates. (Grade B)

Positioning of catheter There is insufficient evidence for more specific recommendation regarding the positioning of catheter at the time of embryo transfer. (Grade C)

Interval before withdrawing catheter There is fair evidence based on one RCT and one cohort study to recommend immediate withdrawal of the embryo transfer catheter after embryo expulsion. (Grade B)

Presence of mucus/blood on catheter There is fair evidence based seven cohort studies that the presence mucus on the embryo transfer catheter, once it is withdrawn, is not associated with a lower clinical pregnancy rate or live-birth rate. (Grade B) Given the mixed results, there is insufficient evidence to state conclusively that the presence of blood on the catheter, once it is withdrawn, is associated with implantation or pregnancy rates. (Grade C)

Speed of injection of catheter load Given the paucity of data, there is insufficient evidence to recommend any specific injection speed of the catheter a the time of ET. (Grade C)

Re-transfer of retained embryo There is fair evidence based on the secondary outcome of one RCT, nine cohort studies, and one series that retained embryo in the transfer catheter and immediate re-transfer do not affect implantation, clinical pregnancy, or spontaneous abortion rates. (Grade B)

Bed rest or Ambulation There is good evidence not to recommend bed rest after embryo transfer. (Grade A)

RECOMMENDATIONS Abdominal ultrasound guidance for ET Removal of cervical mucus Use soft ET catheters Placement of ET catheter tip in the upper or middle (central) area of the uterine cavity, greater than 1cm from the fundus, for embryo expulsion Immediate ambulation once the ET procedure is completed

INTERVENTIONS THAT ARE NOT BENEFICIAL Acupuncture Analgesics, massage, general anesthesia, whole systems traditional Chinese medicine Prophylatic antibiotics Waiting after expulsion of embryo for any specific period of time before withdrawing the ET catheter.

references Toth TL, Lee MS, Bendikson KA, Reindollar RH. Embryo transfer techniques, An ASRM Survey of current SART Practices. Fertil Steril 2017; 107:1003-11 Practice Committee of American Society for Reproductive Medicine. Performing the embryo transfer: a guideline. Fertil Steril 2017, 107:882-96