Mild and Natural IVF

Mild and Natural IVF protocols have gained popularity in recent years in many parts of the world. These protocols involve less medications and a simpler process than conventional stimulation IVF.  These protocols also produce lower pregnancy chances per cycle than conventional stimulation IVF (see figure). However, especially in younger patients and those women with very low ovarian reserve who do not respond well to fertility medications, they may offer a good option because these protocols are much simpler and are therefore less expensive. In these patient groups mild and natural IVF protocols make sense. They are more accessible financially allowing the patient to undergo several cycles of IVF. Most important is that live birth rates over several cycles will add up to match and, in some cases, even surpass those achieved in a single conventional stimulation IVF cycle.

Live birth rate per oocyte retrieval cycle for various ovarian stimulation protocols. Based 2014 & 2015 US national data reported by SART.

Kushnir VA, et al. Observational retrospective study of US national utilization patterns and live birth rates for various ovarian stimulation protocols for in vitro fertilization. BMJ Open 2018.

Mild IVF Steps

Ovarian Stimulation

The first step of the Mild IVF process is ovarian stimulation. Oral medication such as Clomiphene and Letrazole and few injections of Gonadotropins (Follistim or Gonal-F or Menopur) are used to stimulate the ovaries to produce a small number of high-quality follicles with eggs. The lead follicles need reach a size of 16mm to 22mm at time of trigger. A trigger medication is than given 35 hours before the egg retrieval. During the ovarian stimulation the patient will need to have several brief monitoring visits for ultrasounds and blood hormone level tests.  

Egg Retrieval & Sperm Collection

The second step of the Mild IVF is egg retrieval and sperm collection. The egg retrieval is usually done under sedation, but some patients prefer to be awake for this procedure which takes up to 20 minutes. The sperm is collected on the day of the egg retrieval; alternatively frozen sperm can be used for fertilization.

Fertilization & Embryo Development

The third step of the Mild IVF is the fertilization of the eggs with sperm. Fertilization of the eggs in the laboratory involves either conventional insemination or ICSI. The decision as to which procedure is best is typically made by the embryologist and doctor based on the patient’s history and quality of eggs and sperm.

The resulting embryos are then cultured in the incubator. Embryos are allowed to develop until either the cleavage or blastocyst stage. At this point the embryo(s) can be transferred into the uterus, undergo preimplantation genetic testing (PGT), and/or be frozen for future use.

Embryo Transfer

The last step in Mild IVF is the embryo transfer. During the embryo transfer, your physician will insert a soft catheter into the uterus and release the embryo(s) under ultrasound guidance.

Supportive medications such as progesterone are used to help support embryo implantation. A pregnancy test is scheduled to confirm implantation.

Natural IVF involves the same steps as Mild IVF except no medications are used to stimulate the ovaries in the first step.

Diminished Ovarian Reserve (DOR)

In most patients low ovarian reserve is related to normal aging while in some it may be due to premature ovarian aging or underlying medical conditions which lead to premature depletion of eggs from the ovaries. Tests that indicate low ovarian reserve are low antral follicle count (AFC), low AMH level, and high FSH level. To treat fertility issues in patients with low ovarian reserve it is very important to identify and address any underlying medical conditions which may include autoimmune, genetic problems and endometriosis. Ovarian stimulation protocols are individualized for each patient to optimize outcomes. Many women who have low ovarian reserve can still produce multiple follicles and eggs with optimal stimulation, which greatly improves chances of achieving a pregnancy. Some women, however, produce very few follicles/eggs despite optimal stimulation with fertility medications. In these cases, approaches such as mild IVF and natural cycle IVF can still offer a good option to achieve a pregnancy.

In Vitro Maturation (IVM)

Only mature eggs (MII) are typically fertilized during IVF. Most fertility centers discard immature eggs which are collected. Our approach at West Coast Fertility Centers is to attempt IVM on all immature eggs in patients who produce relatively few mature eggs. Often these immature eggs will mature in the laboratory within 24 hours of collection if kept in special media. The eggs that reach maturity and can then undergo fertilization by ICSI. This approach is beneficial for patients who produce relatively few eggs, by helping them have more embryos and therefore additional pregnancy chance from their IVF cycle.

IVM can also be useful for women who:

  • Want to take less medications during the IVF process

  • Have polycystic ovarian syndrome (PCOS)

  • Have hormone-sensitive cancers, such as breast cancer

  • Have a high risk of Ovarian Hyperstimulation Syndrome (OHSS)

  • Have severe side effects from hormonal medications

Oocyte Maturity

  • GV = Germinal vesicle (most immature)

  • MI = Metaphase I oocyte (immature)

  • MII = Metaphase II oocyte (mature)

  • Atretic oocyte (degenerating egg, can be due to failure of maturation or post-maturation)