Controlled Ovarian Stimulation and Human Uterine Lavage

The study is a prospective, multi- center, multiple-arm, feasibility study to evaluate the safety and efficacy of the Previvo System in the recovery of embryos.

This study will recruit up to 500 healthy premenopausal volunteers. Subjects will undergo either natural cycle (NC)/intrauterine insemination (IUI), or controlled ovarian hyperstimulation (COH)/intrauterine insemination (IUI) and have the lavage procedure performed 4-6 days post IUI. It is anticipated that embryos recovered will be cryopreserved for future use or donated for future use.

Subjects will be followed up with for up to 30 days after the lavage procedure. All data will be collected on paper CRFs and analyzed by the Principal Investigator and Study Sponsor.

• Uterine lavage (Procedure): embryo recovery from the uterus following either natural cycle (NC)/intrauterine insemination (IUI), or controlled ovarian hyperstimulation (COH)/intrauterine insemination (IUI).

Primary outcomes

• Serious Adverse Event Collection [30-Days]: Assessment of pain during procedure, bleeding experienced during procedure, and infection symptoms experienced subsequent to procedure. Assessment of fluid recovery, fluid loss through cervix, fluid accumulation in the uterus and fluid loss through fallopian tubes.

Secondary outcomes

• Recovery of Embryos [1 Day]: Demonstrate the Previvo Uterine Lavage System's ability to recover embryos from the uterus following either natural cycle (NC)/intrauterine insemination (IUI), or controlled ovarian hyperstimulation (COH)/intrauterine insemination (IUI).

Sex: Female, ages: 18 Years to 40 Years, accepts healthy volunteers

Inclusion Criteria:

1. Premenopausal female 18-40 years of age
2. Physically healthy and reasonably healthy family medical history
3. Having both ovaries with patent fallopian tubes, no known reproductive problems
4. BMI between 18-35 Kg/m2
5. Presence of a normal uterine cavity as assessed by sonohysterogram (SHG), hysterosalpingogram (HSG), or ultrasound
6. Evidence of normal uterine anatomy that would not prevent the introduction of the lavage catheter.

Exclusion Criteria:

1. History of, or presence of hydrosalpinx
2. Addiction to alcohol and/or narcotics
3. Had radiotherapy or chemotherapy
4. Existence of an ovarian cyst at the beginning of cycle with suspicion of malignancy or a large benign cyst
5. Contraindication for oral contraceptive pills or other study medication
6. Clinically significant abnormal basic metabolic panel lab results
7. Positive test or history of any of the following conditions:

   1. Human immunodeficiency virus (HIV)
   2. Hepatitis B infection
   3. Hepatitis C infection
   4. Syphilis (RPR)
   5. Chlamydial pelvic infection
   6. Gonorrheal pelvic infection.
   7. Positive Pregnancy Test
8. Prior IUD for 60 days or less, or one currently in place
9. Allergic to study materials, supplies and medication
10. Any active, uncontrolled, clinically significant medical condition as determined by the treating principal investigator

• Results publication: Najmabadi S, Rivas JL, Angle MJ, Nadal A, Bastu E, Munne S, Carson SA, Buster JE, Nakajima ST. Human Uterine Lavage: First Live Births from In Vivo Conceived Genetically Screened Blastocysts. Adv Ther. 2023 May;40(5):2534-2541. doi: 10.1007/s12325-023-02486-1. Epub 2023 Mar 29. PMID 36988819
• Results publication: Munne S, Nakajima ST, Najmabadi S, Sauer MV, Angle MJ, Rivas JL, Mendieta LV, Macaso TM, Sawarkar S, Nadal A, Choudhary K, Nezhat C, Carson SA, Buster JE. First PGT-A using human in vivo blastocysts recovered by uterine lavage: comparison with matched IVF embryo controlsdagger. Hum Reprod. 2020 Jan 1;35(1):70-80. doi: 10.1093/humrep/dez242. PMID 31886877

• Gheda Sahyun, MA, Study director, Sponsor GmbH