Ozone and Pulsed Electro-Magnetic Field Therapies Improve Endometrial Lining Thickness in Frozen Embryo Transfer Cycles. Three Case Reports

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RESEARCH REVIEW

Ozone and pulsed electro-magnetic field therapies


improve endometrial lining thickness in frozen embryo
transfer cycles.
Three Case Reports

Zaher Merhi, Rajean Moseley-La Rue, Amber Ray Moseley,


André Hugo Smith, John Zhang

REVIEWED BY:
Aakansha Gupta
15/IBT/001
CONTENTS
• INTRODUCTION
• METHODOLOGY
• CASE STUDIES
• CONCLUSION
• LIMITATIONS
• SUGGESTIONS
INTRODUCTION
• Frozen Embryo Transfer : A frozen embryo transfer
(FET) is a cycle in which the frozen embryos from a
previous fresh IVF or donor egg cycle are thawed and
then transferred back into the woman's uterus.

• Importance of Endometrial lining Thickness in


ART: Correct transfer depth and endometrial thickness is
essential for the implantation, pregnancy and live delivery.
An endometrial thickness of more than 5-7mm is required
for the implantation where as an optimal thickness is of
more than 9mm.
THERAPEUTIC APPROACHES INVOLVED:
1. OZONE: A colorless gas made up of 3 oxygen atoms. Its
used as an alternative therapy to improve the body’s intake
and use of oxygen & to activate the immune system. It also
has strong bactericidal, antiviral, anti-fungal, and anti-
protozoal actions.

2. PEMF: Pulse-Electro Magnetic Field Therapy. PEMF which


is a biophysical therapeutic modality therapy that uses low-
level electromagnetic radiation to heal damaged tissues and
bone, to relieve injury-related pain, and even to stimulate
organs. It is an FDA approved treatment process.
ABOUT THE RESEARCH
• In assisted reproductive technology (ART), studies have shown that an
endometrial lining thickness (EMT) <7 mm was found to have a
significantly lower implantation rate compared to an EMT of ≥7
mm.

• The EMT is traditionally measured by a transvaginal ultrasound in the


follicular phase of a natural FET cycle or after preparation with
estradiol treatment in medicated FET cycles.

• Several treatment protocols for inadequately thin endometrium


include hormonal manipulation by estradiol (oral, vaginal,
transdermal, or intramuscular),vasoactive agents such as low-dose
aspirin, tocopherol (vitamin E),pentoxifylline,vaginal sildenafil,and
others such as tamoxifen,granulocyte-colony-stimulating factor (G-
CSF), and stem cell therapy.
TREATMENT USED (METHODOLOGY):
Ozone Sauna Therapy (OST) protocol using the Hyperthermic
Ozone and Carbonic Acid Transdermal Technology (HOCATT):

• A machine that delivers ozone transdermally (ozone 1 setting at 500


ml/PM in our patients) and vaginally (ozone 2 setting at 200 ml/PM in
our patients) via a silicone tube.

• It includes a chamber, an ozone generator for cabin ozonization, an


ozone generator for simultaneous auxiliary ozone applica- tions, a CO2
administration device and electric CO2 regulator for a CO2 cylinder.

• The HOCATT infuses CO2 gas into the chamber at 5 L/ PM, which will
then mixes with the steam (H2O) in order to form Carbonic Acid
(H2CO3).
• Carbon far infrared ray (FIR) pads (set at 100%), together with
steam, are used to raise body temperature. It also contains a heart
rate monitor, an oxygen humidifier container for pure oxygen
breathing (at 2.5 L/PM) and a Pulsed Electro-Magnetic Field
(PEMF) stand.

• The participant gets completely undressed and sits in the sauna


machine, with the head out in order to avoid breathing the ozone.

• Each participant would ideally have 2 sessions per week for 3 weeks
(total of 6 sessions). Each session is approximately 30 minutes.
The first session starts with 50% ozone concentration which is then
increased to 60% ozone concentration in the second session, 70%
ozone concentration in the third session, and 80% ozone
concentration in the fourth, fifth and sixth sessions.
Figure 1: HOCATT MACHINE
Source of Image:
https://www.google.com/search?q=HOCATT&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiEsfL9
7qzlAhWIfn0KHYVCCJAQ_AUIEygC&biw=1366&bih=657#imgrc=pqgtraVjyuvljM
PARAMETER CASE I CASE II CASE III

INTRODUCTIO 36 year old with 38year old healthy 37year old healthy
N iatrogenic premature patient with severely patient undergoing
ovarian insufficiency. diminished ovarian FET using her own
FET via donor oocyte. reserve. FET via euploid embryos.
donor oocyte.
MEDICAL Controlled type 1 No significant No significant
HISTORY diabetes, Last menses 3 medical history. medical history. A
years ago, Terminated hysteroscopy with
pregnancy once by dilatation and
dilatation and curretage curretage for
menorrhagia.
MALE Normal Normal Normal
PARTNER
SEMEN
ANALYSIS
EXAMINATION Hysteroscopy: Ovaries Sonography: Small Sonography: Normal
PRE- with normal uterus and ovaries with a normal ovaries & uterus with
TREATMENT 3mm EMT. uterus with 3.5mm EMT of 2-3mm with
EMT. Normal areas of EMT 0mm.
hysteroscopy. Normal hysteroscopy.
TREATMENT Evaluation of response to Exogenous Exogenous
(MOCK exogenous hormones for 4 hormones for 2 hormones for 2
CYCLE) weeks via estradiol 4mg- weeks , lining weeks , lining
8mg, no significant reached 4.5mm reached 4mm
improvement, showed maximum maximum
5mm EST. thickness. thickness.
OST 2 sessions of OST/week for 2 sessions of 2 sessions of
TREATMENT 3 weeks, & oral estradiol OST/week for 3 OST/week for 3
daily showed 7mm EMT. weeks, & oral weeks, & oral
estradiol daily estradiol daily
showed 6.7mm showed 6.7mm
EMT. EMT.

POST FET of PGS confirmed FET of Non-PGS A frozen thaw


TREATMENT euploid blastocyst embryo tested blastocyst transfer of a
on 6th day of progesterone. embryo was euploid blastocyst
performed. embryo.
RESULT Single intra-uterine Single intra-uterine Not pregnant.
pregnancy with hormonal pregnancy. At 6
support till 12 weeks of weeks gestation an
gestation. ultrasound showed
Normal Pregnancy. missed abortion.
CONCLUSION:
• A clinical pregnancy includes a missed abortion or a stillbirth. Given
this definition, 2 out of 3 patients presented had a clinical pregnancy.

• In patient #3, even though she had a euploid embryo transferred and a
relatively thick EMT following OST, she did not get pregnant. There is
35% probability of not achieving a clinical pregnancy with a euploid
embryo, which is still not understood.

• Ozone with PEMF constitute a novel experimental approach for


women with persistently thin endometrial lining undergoing FET. It is
a major clinical challenge among fertility patients, which frequently
leads to using a gestational carrier as a last resort.
LIMITATIONS:
• The sample size was small limited to 3 cases
only.
• Lack of a control group.
• Other therapy results should have been
compared with HOCATT.
• More studies are needed to support this
preliminary finding.
SUGGESTIONS:
• Future studies should include randomized trials
with a control group that has not been exposed
to OST.
• Ozone and PEMF levels can be manipulated for
individual cases.
• More therapies in ART can be experimented for
EMT.

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