Conventional IVF vs. Mini IVF
San Diego Fertility Clinic
Minimal stimulation IVF protocols have existed for decades. In fact, in
1978, the first successful IVF pregnancy was the result of a natural cycle—no
stimulation medications were used. The development of conventional IVF
protocols that relied heavily on stimulation medications soon followed.
To understand the advantages of Mini IVF, it is important to understand
the key points of conventional IVF.
A conventional IVF cycle typically consists of three stages:
To maximize the number of eggs being produced (and to inhibit the natural
selection of a single follicle), most IVF clinics require patients to
undergo a preparation stage before the cycle starts.
Preparation for IVF may involve a combination of:
- Birth control pills
- Estrogen pills or patches
- GnRH agonist (Lupron) injections
- and/or testosterone topical gel or patches
There is no uniform consensus regarding which type of medical intervention
is optimal. The primary purpose of the preparation stage is to prevent
a lead follicle from developing, thereby increasing the likelihood of
follicles growing at a relatively similar rate. When one or more follicles
grow at a faster rate than the majority during the stimulation stage,
the physician will typically let them grow past the point of viability—i.e.,
“sacrifice” these dominant follicles—to give the remaining
follicles a chance to mature.
The stimulation stage involves daily injections of IVF medication (such
as Follistim, Gonal-F, or Menopur) at daily doses of 225 IU or more to
stimulate the follicles to grow. IVF clinics follow a range of different
protocols regarding dosage and administration. Some IVF clinics may require
patients to receive injections twice a day (in the morning and night),
or they may prescribe very high daily doses (e.g., 450 IU) to maximize
egg production. Again, there is no uniform consensus regarding which protocol
works best. Generally, the goal for a conventional IVF stimulation protocol
is to promote the development of 10-15 eggs; at some IVF centers, 20-30
eggs is not unusual.
Many IVF clinics adhere to the philosophy that more is better; however,
the clinical evidence does not support this philosophy. The administration
of high doses of IVF medication to maximize egg production leads to an
increased risk of side-effects and other complications. In addition, it
is well accepted that the majority of the eggs retrieved will not develop
into normal embryos.
Premature ovulation, or ovulation before the egg is mature, is an inherent
risk with conventional IVF. To prevent this, physicians may use a GnRH
agonist protocol, which involves the use of Lupron for both the preparation
and stimulation stages. During the preparation stage, Lupron stimulates
FSH and LH production. During the stimulation stage, Lupron shuts down
the pituitary gland’s production of FSH and LH, which in turn can
prevent a premature LH surge and ovulation. A newer protocol, the GnRH
antagonist protocol, uses a GnRH antagonist (e.g., Ganirelix) towards
the end of the cycle to temporarily inactivate the pituitary gland’s
production of LH and FSH.
Prior to retrieval, human chorionic gonadotropin (HCG) is given as a trigger
to release the egg and initiate the ovulation process. The use of HCG
is meant to mimic what happens naturally when the body is ready to ovulate
and the pituitary gland produces a surge of LH: the hormonal surge releases
the egg from the follicle wall into the follicle, the follicle ruptures
and releases the egg 38-40 hours later.
Some IVF clinics may use a GnRH agonist such as Lupron or a combination
of HCG and Lupron as a trigger. Because Lupron remains in the body for
only a few hours and primarily affects more mature eggs, it may decrease
the risk of Ovarian Hyperstimulation Syndrome (OHSS). General anesthesia
is used to sedate the patient for the retrieval procedure, which requires
the presence of an anesthesiologist.
Twenty years ago, physicians in Japan reassessed the viability of minimal
stimulation protocols, revolutionizing IVF treatment by developing what
is now known as
Mini-IVF or Japanese IVF.
Mini-IVF follows what is known as a Clomid hyperstimulation protocol. Patients
are administered Clomid as a daily oral pill in conjunction with a limited
number of FSH injections (approximately 3-6 injections). Clomid stimulates
the natural production of FSH, which lessens the need for stimulation
medication. Clomid also suppresses the LH surge, which minimizes the risk
of premature ovulation and eliminates the need for continued injections
of Lupron to control premature ovulation. Because fewer follicles are
stimulated in a Mini-IVF protocol, egg retrievals are significantly less
complicated and can be performed under local anesthesia. Eliminating the
use of general anesthesia reduces general-anesthesia-related costs as
well as numerous associated side effects and complications.
Single Embryo Transfer
Mini-IVF also incorporates the use of intracytoplasmic sperm injection
(ICSI). To minimize the risks of complications due to multiple gestations,
single embryo transfers are performed. Because a single embryo transfer of a Day 3 embryo is associated
with lower odds of success compared to multiple embryo transfers, embryos
are cultured to the blastocyst stage. Transfer of a single blastocyst
yields equivalent success rates as transferring 2-3 Day 3 embryos.
Due to concerns about the negative effects of Clomid on the uterine environment,
Mini IVF protocol involves “vitrification,” a rapid freezing
technique, which allows the embryo to be transferred to the uterus at
a later date. Vitrification has up to a 99% success rate and has since
been universally adopted as the freezing technique of choice.
The pioneering Mini IVF research in Japan has led to several important
- Not every cycle results in eggs that will produce a normal embryo
- The lead follicle in a cycle contains the egg that is most likely to produce
a viable embryo
Most of the eggs retrieved in conventional IVF cycles will
not produce embryos that reach the blastocyst stage
- The blastocyst rate (i.e., the percentage of eggs that will reach the blastocyst
stage) is much higher in patients who follow minimal stimulation protocols,
since fewer poor-quality eggs are generated. This outcome further supports
the theory that the leading follicles produce the best quality eggs.
IVF clinics specializing in minimal stimulation techniques have been able
to achieve success rates comparable to those seen at conventional IVF
clinics. Mini-IVF has the added advantage of reducing the side effects
and complications that are associated with general anesthesia and high
doses of IVF medication.