Pioneer of infertility treatment. Covering the needs of infertility from various tests 
to IVF/ICSI’s Advanced Reproductive Technologies.

Ovulation Induction Method of IVF

For IVF(in vitro fertilization) we want to retrieve many good quality oocytes, but for success we need to choose suitable protocols.  Ovulation induction is when we allow the follicles to develop and control their maturation until retrieval.  Therefore, choosing an adequate ovulation induction method is a very important step.  There are many ovulation induction methods below, we will discuss the many factors involved in selecting the method that matches the patients needs.

 

  • Pituitary Hormone(FSH LH)
  • Ovarian Hormone(E2 P4)
  • AMH
  • Age
  • Male factor(semen observation, age)
  • Previous Oocyte Pick-up Cycles
  • Possible number of visits
  • Whether or not there is a limit on the oocyte pick-up day
  • Either one or both members of the couple live far away or overseas

 

I will discuss the advantages and what should be taken into account, including cost.

 

> Cost Simulation


 

Stimulation Method

 

The FSH⁄ HMG injection is administered from the 3rd day of menstruation(CD3).  The type of injection and dosage will vary from patient to patient.

 

As a general guideline, 150 units for those in their 20’s, 150-300 units for 30’s, 300 units for Mid-30’s-40’s, and 450 units for those with no response(Gonal F®and other recombinant products will be set at a slightly less amount.).  It is possible to measure the follicle size, and adjust the stimulation or dose to control the number of eggs to be collected.
We will make use of Agonist(mainly a nasal spray, rarely an injection) and Antagonist(abdominal skin injection) as methods to suppress the ovulation before the pick-up of oocytes.

 

Depending on when you start the Agonist, there is the Short Method, Long Method, and Ultra Long Method. Recently, we have introduced a new method using the medroxyprogesterone acetate(MPA).


The Short Method starts from the first day of menstruation(CD1), the Long Method starts from the previous cycle’s mid-term highest temperature, and the Ultra-long Method starts many months before.

 

For Antagonist 3mg will be taken on the 6th day of menstruation(CD6), and thereafter every 4 days until the oocyte pick-up is decided.

 

Oral medications of the HMG-MPA Method will be combined at the time of ovulation induction at 10mg/ day.

Advantages · Many eggs retrievable.
· Easier to ensure frozen eggs.
· The inner membrane of the endometrium will not become thin like it does with Clomifene.
· Can control the number of developing follicles.
· Few empty follicles after ovulation(especially cases after use of Agonist, there are seldom empty follicles).
Points to consider · It is necessary to come everyday to the clinic for an injection(However, self-injection and injection from a closer facility is possible).
· There could be a case of OHSS(ovarian hyper stimulation syndrome).
· As for cases when the number of follicles are many(we aim for about 10 at our clinic), in order to avoid OHSS and because it will mean cryopreservation of all the embryos, usually we don’t do an embryo transfer in the same cycle.
Suitable for · People who want to have many eggs retrieved.
· People who want to have cryopreserve many embryos.
Cost Increasing the amount of injections, and because we will be cryopreserve more eggs, the cost in regards to the oocyte pick-up will become more expensive, but, on the other hand, you will have only one or fewer oocyte pick-ups.

 

Below, we will talk about the various advantages and drawbacks, in regards to stimulation cycles.

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■Agonist Method

· Short Method

Advantages · The flare up of the pituitary hormone(instigating rebound by being suppressed once) can be used for follicle development within 2-3 days of using an Agonist.
Points to consider · Because we can’t use Agonist as a oocyte maturation method and we will be using hCG, there is a possibility of developing OHSS.
· When ovarian reserve is low, the suppression will work too well and follicle development will worsen.
Suitable for patients who maintain ovarian reserve even to some extent.
Remarks There is also the Ultra Short Method that uses only the redound after using an Agonist for 2-4 days but in that case, it will be necessary to take Antagonist for the ovulation suppression.

Schedule

Ovulation Induction Short Method Schedule

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· Long Method

Advantages · Due to the start of the ovulation induction medicine after completely suppressing the pituitary hormone, the follicle development will become equal.
· Hardly any chance of ovulation.
· Control of the oocyte pick-up day is easier.
Points to consider · The amount of injections will increase because of the complete suppression of the pituitary hormone.
· If the ovarian reserve is low, then follicles will not grow.
· Contraception in the previous cycle is necessary.
· For the oocyte maturation method, due to the situation that we can’t use the Agonist and we will be using hCG so there is a chance of developing OHSS.
Suitable for · PCO
· younger patients
· Patients who need to control the oocyte pick-up day.

Schedule

Ovulation Induction Long Method Schedule

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· Ultra Long Method

Leuplin®, Busercur®, Suprecur® Image

We will start the ovulation induction after we have completely suppressed the pituitary hormone, which will take a few months.  We will start the injections after when menstruation will not start. For the pituitary suppression, we use Leuplin® injections, and nasal sprays Busercur®, and Suprecur®.  It is the same as the Long Method.  It is often done in order to fix the implantation environment for those with endometriosis, especially adenomyosis.


Advantages · Improvement of implantation environment of those with endometriosis
Points to consider · If there is a low ovarian reserve, then the follicles will not grow
· Pituitary suppression will continue for a while
· The amount of injection will increase because of complete suppression of the pituitary hormone
Suitable for · Endometriosis
· Uterine myoma

Schedule

Ovulation InductionUltra Long Method Schedule

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■Antagonist Method

· HMG Cetro Method

Cetrotide®(also Ganirest®) Image

The HMG injection will start from the 3rd day of menstruation(CD3).  An abdominal injection of Cetrotide®3mg will be used from the 6th day of menstruation.  Until the decision of oocyte pick-up day and after the follicles are well developed, every four days there will be additions.


Advantages ·It will not suppress the pituitary hormone, when compared to the Agonist Method, it is easier for follicles to develop. 
· Some as Agonist, it is one-time use, and the Pituitary suppression will not last long.
· If there is a risk of OHSS, we will not use hCG for the oocyte maturation, and use the Agonist Nasal Spray instead.
Points to consider · When follicle development is slow and because the price of Antagonist is high, the cost is more expensive.
· Compared to Agonist, there is a slight possibility for ovulation to happen.
Suitable for · For patients who have less than 3 developed follicles using the Short Method.

Schedule

Ovulation Induction HMG Cetro Method Schedule

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■HMG-MPA Method

·HMG-MPA Method

HMG injections and oral medications will start from the 3rd day of menstruation(CD3).


Advantages · Due to the cheap cost of oral medications, fees will be kept low. 
· If you use self-injections, then there will be fewer restrictions on when you come to the clinic. 
· Because it will not suppress the pituitary hormone, compared to the Agonist Method, it is easy for the follicles to develop.
· Some as Agonist, it is one-time use, and the Pituitary suppression will not last long.
· If there is a risk of OHSS, we will not use hCG for the oocyte maturation, and use the Agonist Nasal Spray instead.
· It is possible to have the "Random Start Method" that can have ovulation induction done regardless of the menstruation cycle.
Points to consider · A fresh embryo transfer cannot be done.
· Compared to Agonist, there is a slight possibility for ovulation to occur.
Suitable for · Patients that want to decrease visits to the clinic.
· Patients that come from afar, before breast cancer treatment, or needing emergency ovulation induction, etc. for cases of Random Start Method. 

Schedule

HMG-MPA Method Schedule

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Low˜ Medium Stimulation Method

 

· Complete Natural Cycle

Usually, regardless of oral medicine and injections, we will not use ovulation induction medicines. However, there are times when we will use Antagonist or HMG, 1-2 times to prevent ovulation before the oocyte pick-up.

Advantages · The number of times you will need to come in to outpatient are few.
· There are fewer burdens on the body because we do not use ovulation induction medicines.
· Possible to do back-to-back oocyte pick-ups cycles.
Points to consider · It is impossible to do if your menstruation is irregular.
· The number of oocyte pick-ups will increase.
· Sometimes when the follicles are empty.
· There are times after ovulation when we can’t do an oocyte pick-up.
· There are times when we will not be able to freeze the embryo nor perform an embryo transfer when fertilization and or division did not go well because we can only do the oocyte pick-up once.
Suitable for · Over 44 years of age, decline of the ovarian reserve, low AMH etc., and those who request this method.
· When there is a high value of FSH
Cost The cost is lower than usual for the oocyte pick-up, and it is often the case that even if only 1 egg is retrieved from the pick up the cost for cryopreservation is unnecessary.

Schedule

Ovulation Induction Complete Natural Cycle Schedule

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· Clomifene(Clomid®, Serofene®)

Clomifene Image

Medication starts from the 3rd day of menstruation(CD3).  The number of follicles can be adjusted through HMG injection combined with Cetrotide.


Advantages · Lower number of visits because it is an oral medicine
· Back-to-back oocyte pick-ups possible
· 1st selection of PCO
· For 1 cycle the cost is low because the number of the oocyte pick-ups and the number of frozen eggs is less
· If it is unsuccessful, for every 2-3 cycles, the cost will become a little more expensive because there will be an implementation after oocyte pick-up.
Points to consider Usually a frozen embryo transfer is done on a different cycle because the inner membrane of the endometrium will become thin.
Suitable for · Patiente who reguest a natural method but if possible who would want to take 2-3

Schedule

Ovulation Induction Clomifene Schedule

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· Sexovid®

Sexovid® Image

Medicine name: Cyclophenyl. This is a non-steroidal ovulation induction medicine that has a weak estrogen effect. It is said to affect the pituitaries and encourages the secretion of gonadotropin, but there are still many unclear points. When compared to Clomifene, the effects of the ovulation induction are weak. We might also use it jointly with injections during the process. Medication is taken from the 3rd day of menstruation(CD3) for 5 days.


Advantages · Fewer number of clinic visits because it is an oral medicine
· Back-to-back oocyte pick-ups possible
· Usually the embryo transfer can not be done in the same cycle because the inner membrane of the endometrium does not become thin as when compared to Clomifene.
Points to consider · The effects on ovulation induction are weak, will usually get around 1 developed follicle.  We can’t use cryopreservation.
· When compared to Clomifene, the follicles are small and it's easy for an LH surge to happen, and there is a high risk of ovulation before oocyte pick-up.
Cost It is about the same as a complete natural cycle.

Schedule

Ovulation Induction Sexovid® Schedule

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· Femara®(Anastrozole®)

Femara®(Anastrozole®)

Medicine name: Retrozol.  It was originally used as a treatment medicine for postmenopausal breast cancer.  Within the ovaries, because we will inhibit the aromatase that has the enzyme necessary for when the male hormone is exchanged with oestradiol, it is said that the generation of oestradiol is suppressed and ovulation is induced when the secretion of FSH has risen by negative feedback, but there are still many unclear points.  It is used just as Clomifene, from the 3rd day of menstruation(CD3).


Advantages · Effects of the anti estrogen are few, and the inner membrane of the endometrium will not become thin.
· Even where the ovarian reserve is depleted and the Clomifene doesn’t seem to be working, there are cases of follicles developing.
Points to consider · Use as an ovulation inducing drug is still not generally accepted.
Suitable for · Non development of follicles by Clomifene
· History of Breast Cancer

Schedule

Ovulation Induction Femara Schedule

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· HRT-OPU Method

Direction to expect follicle development by taking estrogen and the results of the Rebound Method.

Suitable for · Those whom have difficulties with follicle development

Schedule

Ovulation Induction Estrogen Rebound Schedule

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Cost Simulation

 

 

❈The costs are a simulation from a treatment model.

❈The prices are subject to change without notice.

 

 

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Oak Medical Group has been from the time we opened, supporting the many issues of women's health, building performance and trust, and not only here in Osaka, but centering in Kansai we are receiving patients from across Japan.
Especially with our infertility treatment, we are widely covering the various tests to IVF/ICSI's Advanced Reproductive Technologies.  Depending on the cause of the infertility, we are handling the treatment of each patient one by one.  If you have some concerns, please don't hesitate to consult with us.