Assisted Reproductive Technologies (ART) range from simple ovarian stimulation with Intra- Uterine Insemination (IUI) to conventional In Vitro Fertilization (IVF) which may be combined with Pre-implantation Genetic Screening (PGS) of embryos and subsequent Frozen Embryo Transfer (FET). There is a 10-fold difference in cost between the low tech IUI and the high tech IVF. The goal of ovarian stimulation in IUI is to produce 2-3 follicles (follicles are the structures in the ovaries with eggs inside). Around day 12 of the cycle an ultrasound is performed to assess the number of follicles produced. HCG is used to trigger the release of the eggs for insemination on day 14. It is really quite simple. If a patient does not get pregnant, there are several unanswered questions, however. Did the eggs get released? Did the eggs get fertilized? Did embryos form and develop?
Another concern with IUI is multiple pregnancy. IUI costs much less than IVF, but has a lower per cycle pregnancy rate and a higher risk of multiple gestation. The goal of IVF stimulation is very different than IUI. IVF involves taking substantially more medications, often producing 10 or more eggs. We will eventually put back one or two embryos, so multiple pregnancies are less of a concern, though twins do happen. The major reason for the cost differential is the expense of the medications, monitoring, laboratory and the staffing.
We feel that the INVOcell device may bridge the financial and technology gap between IUI and IVF. A recent publication compared the pregnancy rates with the device compared to traditional IVF and it was similar. The stimulation protocol used in that study had fewer ultrasound exams, but the same amount of medicine (i.e. Lupron with 1800 IU of FSH on average) and may have still been costly depending upon the cost of the medications, but certainly less expensive than traditional IVF. Other studies have used more minimal stimulations with good ongoing pregnancy rates.
Is INVOcell™ for everyone? We feel that patients with good ovarian function (i.e. AMH >1.0), adequate sperm concentrations (i.e. >2 million/ml), and those not requiring many oocytes (i.e. not doing PGS) would be ideal candidates. Consultation with our Physicians will help patients understand if this is a reasonable course of treatment. This procedure is not covered by insurance at present, so it is for self pay patients only.
Overview of the INVOcell™ Mini IVF process
INVOcell™ has potential benefits:
- Truly unique form of Assisted Reproductive Technology
- FDA Approved Device
- Pregnancy Rates that are equivalent to conventional IVF in some studies
- Well accepted by patients during the studies
- Conception occurs in body, which may be preferable for some patients based upon religious or ethical concerns
- ICSI can still be used if there are concerns about sperm quality or fertilization
INVOcell™ may be a true mini IVF
We consider mini IVF to include less medication and monitoring of the cycle resulting in lower costs to the patient. The INVOcell™ device appears to have the same pregnancy rates as IVF and costs less, so it may be something to consider. If we used the same amount of medications and monitoring as conventional IVF, the cost differential may not justify its use. Cost is the major limiting factor for most patients that are considering ART.
Some sites have mentioned limitations of the technology, albeit before it was approved by the FDA. For instance, fertilization is not checked 18-22 hours post insemination when the eggs and sperm a placed in the device for ‘natural’ fertilization to occur. There is the chance that 2 sperm may fertilize an egg (i.e. triploidy) creating an embryo that may miscarry. While studies showed good fertilization with the basic technique, we feel that it may be better to do ICSI of the oocytes before placement in the device for intra vaginal culture. Fertilization of mature oocytes by ICSI is >80 % in our laboratory. A study using INVOcell™ and ICSI showed similar pregnancy rates compared to IVF-ICSI.
Additionally, with ICSI we would avoid the potential effects of excessive sperm and the granulosa cells that surround the oocyte on the culture media. A concern is that the other cells would consume nutrients that are required by the embryos. The fertilized egg should benefit more from the culture media without other cells negatively affecting it. If we remove the device on day 3, we can do embryo transfer of high quality embryos and/or culture the remaining embryos until day 5 for cryopreservation.
We have high pregnancy rates with the day 3 and day 5 embryo transfer. Assisted hatching can be done in day 3, if indicated. Day 5 transfers can be done when we use continuous single culture media, as was done in one of the studies mentioned above.
Cost of INVOcell™ Mini IVF
As mentioned above, if the cost of the medicines, monitoring, and procedure were significantly below conventional IVF, ART could benefit significantly more couples. For mini IVF, we typically use a combination of fertility pills and shots. Letrozole may be combined with 75 units a day of FSH (Follicle Stimulating Hormone; Gonal-F, Follistim), 150 a day of FSH or 150 a day of HMG (Human Menopausal Gonadotropins; Menopur). These regimens often result in 5-7 eggs. If these latter protocols were given during IUI cycles, the patients would probably make too many eggs and we would have to cancel the cycle. INVOcell™ may be more of a supped up IUI than a full fledged IVF.
Pre-Cycle visits for consents ($100), trial embryo transfer ($300) and infectious disease testing ($200) are not included in the costs for the procedure below.
In summary, the INVOcell™ Mini IVF procedure may fill the gap between IUI and IVF and bring more affordable high tech fertility to patients in need. We are excited to be the first program in the State to offer this unique fertility treatment to our patients.