The INVOcell^TM device is a 2-inch plastic capsule and comprises an inner chamber, an outer rigid shell, and a retention system. The parts of the INVOcell^TM are best shown in (Fig. 19.2). The inner chamber and the outer rigid shell are made from biocompatible plastic material (polypropylene) which is permeable to CO₂ gas and O₂ gas. The polypropylene material enable CO₂ gas and O₂ gas permeate the inner chamber wall from the vagina into contained culture medium. The INVOcell^TM device is ISO-10993 tested to assess toxicity, biocompatibility, comfort, and retention within the vaginal cavity [2]. Description of each INVOcell^TM part is as follows:

INVO procedure has contributed to a returned interest in natural and more physiological IVF protocols that produce less embryos and are safer for the female. Using INVOcell^TM allows maturation of gametes, fertilization, and embryo development into the best natural incubator, the vaginal cavity. This alternative option for conventional IVF treatment is considered as a simplified replacement of the IVF complex laboratories. This has reduced the necessity of sophisticated laboratory instrumentation simplifying the process of IVF and embryo development. Natural cycle and mild stimulation protocols with the INVO procedure also have contributed to the simplicity, low complication rates, and low cost of the INVO cycle.

The monitoring of natural cycle is simple and inexpensive. Our modified natural protocols begin at the first day of the menstrual cycle evaluating the ovarian reserve by a pelvic ultrasound examination. On day 7th of menstrual cycle, a pelvic ultrasound is made to evaluate follicular size and also to identify a possible dominant follicle. At that moment, we start clomiphene citrate (CC) at doses of 25 mg per day (good ovarian reserve) or 50 mg per day (low ovarian reserve) at 9 am for 5 days to reinforce the follicular recruitment. At 13th day of the menstrual cycle, we start indomethacin (50 mg every 8 h per day, as used in mild protocols and discussed later) if the leading follicle reached 15 mm of diameter and is used to prevent premature ovulation. Triggering of ovulation is performed by GnRH-a (injection of 1 mg of leuprolide acetate) when the size of the follicle reaches 17 mm and the blood estradiol levels are around 250 pg/ml. Oocyte retrieval is performed 36 h after ovulation trigger and continues with the INVO laboratory protocol.

Seven years ago, the conventional protocols using high doses of gonadotropins have been discontinued in our clinic. At present, we have designed a new era in assisted reproductive (AR) techniques. Our main goal is to offer more physiological, natural, and safe treatments. This new alternative in controlled ovarian stimulation (COS) has been achieved by using low and mild doses of hormonal medications that support affordable treatments with the purpose of reaching a significant number of infertile couples in our population in terms of cost–benefit. Mild IVF and INVO procedure offer an advantage simplifying the laboratory equipment and manipulations needed, which might decrease the costs and allow a widespread application for patients who cannot afford traditional IVF [20] as it would be the case in developing countries, where the access to cost-effective infertility treatment is limited. We have focused on the following important factors for protocol preparation:

Different purposed methods of mild COS have been designed based on the global scientific evidence and joined to adjuvant therapies as hyperbaric oxygen sessions and preconceptional preparation cycle that enhances the effectiveness of AR treatments.

HBOT consists of the medical use of oxygen at high doses (oxygen saturation close to 100%), during short periods of time (generally one hour), and at level higher than atmospheric pressure (oxygen pressure comparable to the sea level). The patient breathes pure oxygen in a pressured chamber that induces positive effects to the uterus such as:

As a part of COS treatments, we have suggested strategies of previous preparation using birth control pills. Those pills should be started at the first day of the menstrual cycle throughout 21 days. Once the patient takes the 21st pill of preparation, we start the administration of estradiol valerate 2 mg (tablets) for three continuous days. The bleeding will occur on a scheduled basis on the 26th and 29th days of the menstrual cycle. The main goal is to harmonize the FSH and LH levels, the follicular development, and the oocyte–endometrial quality. Also, preconceptional preparation allows a regular endometrial desquamation reducing the possibilities of ovarian cyst formation that impedes the beginning of COS (Fig. 19.3).

We have established different protocols based on the concentration of medications used for ovarian stimulation: clomiphene citrate (CC) and human menopausal gonadotropin (hMG) and the total days of treatment (Fig. 19.4).

On IVF mild protocols, we have established the use of nonsteroidal anti-inflammatory (NSAID) medicines derived from the indol-3-acetic acid. These medicines, such as indomethacin or acemetacin, are non-selective inhibitors of the production of potent inflammatory mediators derived from COX-2 enzimatic action. COX-2 molecule is essential for the biosynthesis of prostaglandins E2 (PGE2) and F2 (PGF2). Prostaglandins are molecules derived from fatty acids stored in the cell membrane, and its biosynthesis can be divided into three phases: 1) releasing of arachidonic acid from the membrane phospholipids by the phospholipase enzyme action, 2) conversion of the arachidonic acid into an unstable intermediate prostaglandin called PGH2, by the action of COX-2, and 3) conversion of the PGH2 molecule in different specific active prostanoids for each cell [21]. Acemetacin and indomethacin have inhibitory action over COX-2 molecule. Prostaglandins are critical mediators of many biological procedures involved in female fertility such as ovulation, luteolysis, embryo implantation, and delivery [21]. The close relationship between LH surge and PGE2 and PGF2 concentrations in the ovarian follicles, just previous to the ovulation, suggests that the granulose cells might produce those two molecules. Acemetacin and indomethacin have a direct effect on the ovary inhibiting the preovulatory concentration of PGE2 and PGF2 into the follicle giving raise to a lag of oocyte releasing. Also, all molecular events involved in the follicular rupture including increased vascular permeability, collagenolysis, and local inflammatory events are inhibited.