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In this section, I will cover briefly some of the common treatment options available for the management of difficult infertility cases. I will not cover the use of fertility drugs such as clomid for ovulation induction in women with ovulation problems and irregular cycles. Please have a chat with Dr. Leong about this.


 

Cryopreservation – ovary, eggs and sperm

Reproductive tissues such as ovary, human eggs and sperm can be frozen for future use. The technology used in the cryopreservation of such tissues has improved over the past few years allowing harvested ovary, eggs and sperm to be stored under liquid nitrogen.

Patients facing chemotherapy for cancer have the options of either having their ovary harvested by laparoscopy (key-hole surgery) and then frozen in small pieces or undergoing IVF treatment (if time permits) to have a number of eggs retrieved for freezing. In the case of egg freezing, medicare will subsidise such IVF treatment as there is a recognized medical indication. Eggs may also be harvested after follicle stimulation in an IVF cycle for freezing for social indication such as a career woman wanting to delay motherhood. Whilst it is preferable for the woman not to be dependent on egg freezing to secure her chance of motherhood in the future as success may never happen, egg freezing does offer some insurance against potential childlessness. It is important to note that medicare will not subsidise for social egg freezing and there is a large out of pocket expense. However there are many conditions that are considered medical indications suitable for egg freezing. Please discuss with Dr. Leong.

For men, sperm freezing can also be undertaken prior to starting chemotherapy, vasectomy, undergoing IVF treatment and if considering sperm donation or for other reasons. There is usually a small fee for freezing and storage of sperm unless for sperm donation which is free.

Technically speaking, the reproductive tissues can be frozen for eternity however we don’t have long term data about the quality of the gametes beyond a decade or so of freezing.

Donor egg and sperm

The world’s first baby conceived via egg donation was born in 1983. The pregnancy was a result of IVF performed by world renowned Monash IVF. Since then, conception via egg donation has become common place. Some of the women who require egg donations are:

  • Women who had unfortunately undergone premature menopause.
  • Women who carried a significant risk of fetal abnormality if conceived with their own eggs.
  • Older women (> 40 yo) who have undergone several cycles of IVF without success.
  • Menopausal women between the ages of 45-54 yo.

Egg donors are either anonymous or known to the recipient and must be generally between 25 to 38 years old. Most donors are fertile women who donate altruistically to a known recipient e.g. sister, niece, close friends or non-blood relatives. Altruistic donors can also be strangers who hear the ‘call’ of the recipients through advertisements in selected newspapers. However, an approval must be sought from VARTA (Victorian Assisted Reproductive Treatment Authority) before one is allowed to place an advertisement for an egg donor. Please contact the egg donor coordinator at Monash IVF (03) 9429-9188 begin_of_the_skype_highlighting FREE (03) 9429-9188 end_of_the_skype_highlighting for more information.

Both the donor and recipient must start the IVF treatment together, usually commencing on the oral contraceptive pill at the same time. The donor will need to inject herself with hormones to stimulate her ovaries to produce eggs and then have them collected under a light general anaesthetic. This procedure is performed using a probe inserted in the vagina under ultrasound guidance. All available eggs will be retrieved and then fertilized with the recipient partner’s sperm. Once fertilized, the embryos will be cultured generally to day five and a single embryo is transferred back into the uterus of the recipient. The recipient will require to use hormones consisting of nasal spray (synarel) or an injection called Lucrin followed by special hormone tablets to thicken the uterine lining. Once the lining has achieved a certain thickness it becomes receptive and ready to accept an embryo. About twelve days after the embryo transfer, a pregnancy blood test is performed.

One in eight infertile couples requires the use of a donor sperm to achieve a pregnancy. Single women or those in same sex relationship may choose a sperm donor to help them achieve a pregnancy. Sperm donors can be selected from Monash IVF’s sperm donor bank or recruited independently by the recipient. For more information please click on the link below: http://www.monashivf.com/Services/Donor_Programs1/Donor_Sperm_Program.aspx

Ovulation induction and intrauterine insemination (OI IUI)

This is one form of Assisted Reproductive Treatment and involves a daily injection of a low dose hormone known as FSH (Follicle Stimulating Hormone which is part of the gonadotropin family) to stimulate the ovaries to produce one to two follicles. The follicles are then monitored as they grow by regular blood tests and ultrasound scans. Once the follicles have attained the right size, another injection of HCG hormone known as the “trigger” is given to mature the egg(s) and induce ovulation approximately 38 hours from the time of administration. Semen is collected by ejaculation and then processed through a special gel gradient to select the most motile and good quality sperm. This final concentration of motile sperm is then injected into the woman’s uterine cavity via a fine catheter, timed 38 hours from the trigger injection.

This type of assisted reproductive treatment is employed for women with irregular ovulation and have not responded to treatment with an ovulation induction medication such as clomiphene. About 80% of women will respond to clomiphene and the remaining usually respond to FSH hormone. Men with mild sperm defects may also benefit from OI IUI because the processed sperm may overcome minor defects such as mild low motility, mild sperm antibodies and mild abnormal forms. Couples who are not having adequate timed intercourse because they often spend time apart e.g. a spouse’s frequent travel for work, may also benefit from this type of treatment. OI IUI is often perceived as being less invasive than IVF which is accurate on some levels but in essence is really not that different. It carries a higher risk of multiple pregnancies such as twins and triplets compared with clomiphene. This method works well for women who have trouble ovulating regularly and studies showed that in the absence of other fertility problems, it was able to normalize a couple’s chance of conceiving. However, if the woman is already ovulating well and there are no other obvious reasons e.g. unexplained infertility, then the chances of conceiving with OI IUI are not going to be significantly higher with this method. Couple with this problem tends to benefit more from IVF. However, many other important factors must be taken into consideration before deciding on the right course of treatment.

In-vitro fertilisation

IVF has come a long way since its beginning over thirty years ago. Louise Joy Brown was born on July 25, 1978 as a result of pioneering work by Dr Steptoe and Dr Edwards in the UK. This was the first time an infertile woman with blocked fallopian tubes was able to have a baby using this scientific method. Monash IVF achieved the world’s first pregnancy by IVF but unfortunately the pregnancy resulted in an early miscarriage. Subsequently Monash IVF achieved quite a few groundbreaking achievements-

  • First frozen embryo birth in the world
  • First donor egg baby in the world
  • World’s first pregnancy and birth from a sperm retrieval operation
  • Australia’s first surrogate birth
  • Australia’s first open testicular biopsy twins
  • Australia’s first blastocyst baby

So what is In-vitro fertilization or IVF? It is a scientific method of fertilizing an egg outside the human body by mixing a concentration of sperm with the egg in a special medium. This was previously performed in a test tube and hence the name ‘test tube’ baby. In modern times, fertilization is performed in a special dish. The terminology now encompasses the entire process starting from hormone injections, through to egg retrieval, fertilization, embryo transfer and hormonal support.

IVF begins by requiring the woman to start hormone injections on the second day of her menstrual period. The hormone is recombinant FSH administered to stimulate ovarian follicles to grow. Ultrasound scan and hormone blood tests are performed during the stimulation phase to track the progress of ovarian follicular development. Usually after about six injections of FSH, another hormone called gonadotropin antagonist (GnRH antagonist) is co-administered to prevent the ovarian follicles to develop too fast and ovulate prematurely. Once the ovarian follicles have reached a certain size usually about 16-17 mm, a trigger injection of HCG hormone is given to mature the follicles. After 36-38 hours of the trigger injection, eggs are retrieved via the vagina with a fine aspirate needle under direct ultrasound vision. This procedure is usually performed under a light general anaesthetic. The eggs are then assessed for quality and maturity. If fertilization is to be achieved by the standard method, the eggs are then mixed with the processed sperm in a special dish. Success of fertilisation will be checked a few hours later. Sometimes, the quality of sperm is poor and does not allow us to undertake the standard fertilization method. In this case, sperm will be selected individually based on their motility and physical appearances for direct insertion into a mature egg. Each egg is surrounded by a cloud of cells called ‘cumulus’ which must be stripped away before a sperm is microinjected into the egg. Sperm microinjection is also known by the acronym ICSI (Intracytoplasmic sperm injection). Once an egg is fertilized it immediately becomes a zygote. And within a few hours of fertilisation, the intricate and complex genomic machinery becomes activated and cell division starts to gain pace in the fertilised embryo. The embryo starts to form, containing two cells on day one and multiplying every day. By day five, the cells within the embryo become too numerous to be counted and these cells start to organize themselves into regions which eventually develop into the fetus and placenta. The embryo at this stage is known as a blastocyst. Embryo(s) can be replaced back into the uterine cavity (womb) from day two to day six. However they are frequently either transferred on day two/three or day five. Day five embryos tend to be stronger and better quality and by simply selecting the best quality embryo on day five ensures a higher pregnancy rate. A good quality embryo tends to survive to day five whereas the weaker quality embryos tend not to survive that long. Embryos are replaced in synchrony with the endometrial lining so that a day three embryo is replaced day three after egg retrieval and similarly a day five blastocyst is replaced five days after egg retrieval. The human endometrial lining has a fairly narrow window of receptivity to allow for implantation.

Embryo transfer is normally performed with the woman awake. This procedure is akin to the process of taking a pap smear. A vaginal speculum is inserted into the vagina and the cervix is then displayed. A fine flexible plastic catheter is inserted into the cervix up into the level of the uterus. An even smaller plastic catheter containing the embryo(s) loaded in a special medium is then inserted in place and the medium injected into the uterine cavity. This whole process can be seen on ultrasound. Ultrasound guided transfer is best practice and regularly performed at Monash IVF. A vaginal gel containing progesterone e.g. crinone or vaginal progesterone pessary is inserted once or twice daily after embryo transfer to support the endometrial lining until the pregnancy blood test. Sometimes progesterone supplementation is continued to twelve week gestation. If you are pregnant, a pregnancy blood test is repeated weekly until six to seven weeks gestation. At seven weeks gestation, an ultrasound scan is performed to confirm the viability and location of the pregnancy. Please note that by convention a four week pregnancy is taken from the first day of last menstrual period. It does not mean four weeks from ovulation or egg retrieval. It is in fact only two weeks from ovulation or egg retrieval.

There are a few different types of stimulation protocols available. Sometimes you may be started on the pill to regulate your menstrual cycle before starting IVF. Other times, the pill is used to time the onset of your next menstrual period for ease of starting treatment. A different drug called GnRH agonist e.g. synarel nasal spray or lucrin may also be used instead of the GnRH antagonist. Dr. Leong will determine what suits you best depending on your unique situation.

If you have any surplus embryos that are good quality they will be frozen. Day five embryos are now routinely frozen by an innovative method known as ‘vitrification’ at Monash IVF. This is a quick snap freezing method where the embryos are frozen in liquid nitrogen by quickly lowering the temperature down to -196°C. The embryos remain in this suspended metabolic state indefinitely until they are thawed. Technically speaking, they can be frozen for a very long time. The availability of frozen embryos improves your chances of pregnancy as you can have “more than one go” from each stimulated (a cycle where hormone injections are used to stimulate follicular development) cycle.

Frozen embryos are thawed on the day of transfer. One embryo is thawed at a time and normally a single embryo is transferred. Hormonal drugs may be used to artificially create a menstrual cycle if you have irregular periods or sometimes, no drugs are used at all. If no drugs are used, it is known as a natural cycle embryo transfer. The key in natural cycle is to determine when ovulation has occurred and the embryo is then transferred back in synchrony with the endometrial lining corresponding to the number of days it was frozen for. Hence a day five embryo is transferred five days after ovulation.

The information provided here paints a broad overview of IVF and is not meant to be exhaustive.
Please give the following issues some thought and discuss them with Dr. Leong.

  • IVF cycle success rates and average number of cycles to conceive
  • Standard insemination or ICSI
  • Single or multiple embryo transfer
  • Risks and complications of IVF to both mother and baby
  • What is OHSS? (Ovarian Hyperstimulation Syndrome)
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