While IVF offers an effective treatment for infertility, a significant proportion of IVF cycles still result in failed implantation and early miscarriage. As such, new therapies that improve pregnancy outcomes are highly desirable. Both traditional and laser acupuncture during the IVF cycle has become a popular option for women looking to improve their pregnancy rates. However, studies looking to understand the effects of acupuncture on IVF have demonstrated contradicting results. While some studies show an improvement in pregnancy rates in women undergoing IVF with traditional acupuncture treatment, other studies show no difference. Moreover, there are few studies exploring the role of laser and traditional acupuncture in IVF cycles and the studies done thus far have shown no change in pregnancy rates. However, there have been no studies to-date that have looked at women who are receiving IVF for embryos with normal genetics. This is important because embryos with abnormal genetics are a major reason for failed implantation and miscarriage, which can make the effects of acupuncture on pregnancy rates difficult to evaluate. This study is a pilot study looking to better understand the role of laser and traditional acupuncture as a supplemental treatment in women undergoing euploid (normal genetics) embryo transfer. This is the first study to include only genetically normal embryos, which may help to better understand the effects of laser and traditional acupuncture on IVF outcomes.

Purpose:

To assess the feasibility and preliminary outcomes of a single-blinded randomized clinical trial evaluating the effect of laser and traditional acupuncture during the IVF cycle on pregnancy outcomes in women undergoing euploid embryo transfer.

Hypothesis:

A single-blinded randomized clinical trial evaluating the effects and reproductive outcomes of laser and traditional acupuncture during the IVF cycle will be acceptable to patients and feasible for a large fertility clinic.

Justification:

IVF is a costly treatment option for women, their partners, and the public. Therefore, new therapies that improve reproductive and health outcomes are highly desirable. Furthermore, the economic burden of IVF is directly related to the number of attempted cycles, and hence there is a growing interest in the use of adjuvant therapies to optimize pregnancy outcomes on a per cycle basis.

Acupuncture, both traditional and laser, has become a popular adjuvant therapy for women undergoing IVF treatment. Previous studies attempting to validate the effects of traditional acupuncture on IVF outcomes have demonstrated contradicting results. Importantly, none of the prior studies controlled for the effect of embryonic aneuploidy, which is a major contributor to implantation failure and early miscarriage. Further, there are very few studies assessing the effects of laser and traditional acupuncture on IVF outcomes and no studies to date that take into account embryo genetics.

Hence, the purpose of this study is to investigate the feasibility of a randomized clinical trial assessing the effects of laser and traditional acupuncture on IVF outcomes in women undergoing euploid embryo transfer after complete chromosomal screening, thereby controlling for a normal karyotype and allowing for a more meaningful analysis of the effect of laser and traditional acupuncture on IVF outcomes.

Objectives:

1. To assess patient acceptance and clinical feasibility of a well-designed randomized clinical pilot study comparing the effects of a clinical-dose (8 total sessions) of laser and needle acupuncture on pregnancy outcomes in IVF.
2. To generate preliminary results based on a feasible study design that may inform the implementation of a larger randomized clinical study in the future.

Research design:

One hundred patients undergoing IVF with preimplantation genetics screening will be randomized using a computer-generated block randomization method to either the laser and traditional acupuncture (n = 50) or standard-of-care (n = 50) arm. The laser acupuncture arm will be offered treatment 3 times a week starting from menses, plus an additional treatment before embryo transfer (ET). The goal is to have completed 7 treatments prior to ET, for a total of 8 treatments (last treatment done at Olive Centre right before ET). Patients in the standard-of-care arm will receive standard treatment. Physicians and nurses will be blinded to the groups assigned and will provide the same standard of care to both groups. Participants will be asked to complete a short survey following each laser acupuncture treatment.

Study procedure:

Participants in the laser and needle acupuncture arm will be offered treatment 2-4 times a week starting from menses, plus an additional treatment before ET. The goal is to have completed 7 treatments prior to ET, then one one on the day of ET (before and after transfer), for a total of 8 treatment sessions. Participants will be asked to complete a short survey following each laser and traditional acupuncture session.

Because the results of the preimplantation genetic screening (PGS) do not return with enough time for a fresh embryo transfer, all PGS embryos are transferred as part of a frozen ET. Unfortunately, there are no consensus protocols on the use of acupuncture in either frozen or fresh embryo IVF transfers. As such, we have used the expert opinions of several registered acupuncturists skilled in reproductive health to arrive at a consensus laser acupuncture protocol that is appropriate for a frozen-embryo transfer. Full details of the protocol are included in the Research Proposal.

Laser and traditional acupuncture will be performed by a certified acupuncturist skilled in reproductive health and experienced with use of laser and needle acupuncture in IVF. Physicians and nurses will be blinded to the groups assigned. The following certified acupuncturists will be performing the acupunctures:

Lorne Brown Ryan Funk Emilie Salomons Christina Ceconni Allison Locke Kathleen Lee Bronwyn Melville There are fewer variables with laser acupuncture than traditional acupuncture. The amount of energy and distance from each acupoint are the same, so there is less variation between providers. With traditional acupuncture, there is difference in needle depth of penetration, pressure, etc. Additionally, while it would be ideal for the same acupuncturist to provide all the treatment, this isn't feasible for the acupuncture clinic.

The reference arm will receive standard treatment.

The questionnaire surveys will be given to the patient participants after each laser acupuncture session if they are in the acupuncture group, and after their embryo transfer if they are from the standard care group. The study participants will be taken to a different room/office within the clinic to complete the surveys. To ensure blinding, the questionnaires will be provided by research staff not involved in the direct care of the patients. After completing the survey, the participant will place it in a sealed envelope.

This way, the participant responses are anonymized, with only the participant identification number on the forms, and no other patient-identifying information. The responses will not be made known to the physicians and nurses.

Statistical analysis:

Feasibility outcomes to be assessed include recruitment rate, refusal rate, retention rate, non-compliance rate, ability to maintain blindedness of healthcare staff, inclusion of all important data points, and determination of centre willingness and capacity.

Success of feasibility will be determined by the following criteria:

• At least 70% of all eligible participants choose to participate
• At least 90% retention of those that choose to participate
• At least 90% of all recruited participants complete six acupuncture sessions and the follow up survey
• At least 95% maintained blindedness of healthcare providers

Inclusion Criteria:

• use of preimplantation genetic screening
• treatment with IVF/intracytoplasmatic sperm injection (ICSI)
• age <40
• BMI <35

Exclusion Criteria:

• three or more prior failed IVF cycles with euploid embryo transfer
• known structural or anatomic causes of infertility
• male factor infertility
• patients already receiving concomitant treatment within the last 3 months (e.g. reflexology, acupuncture, herbal supplements, meditation).

The de-identified research data will be deposited into a publicly accessible database after publication. This data includes demographics, treatment protocols, pregnancy outcomes, and other research-related information. At no time will identifying information, such their names, birth dates or street addresses be included in such data.

Data will be available within 6 months after the completion of the study.

Data access requests will be reviewed by an external independent review panel. Requestors will need to sign a Data Access Agreement

Participants will be assigned a computer generated code to be used on data collection forms.