Treatment for Infertility
4.1. Treatment for infertility
4.1.1 Ovulation Induction (OI)
For various couples, simple treatment may be as effective as very advanced assisted reproductive technology (ART). For example, having timed intercourse during ovulation would enhance the chance of pregnancy.
The chance for pregnancy can be further improved by ovulation induction using infertility medications combined with timed intercourse. There are both medications in oral and also injectable form to stimulate the development and release of eggs. These include clomiphene citrate, highly purified human menopausal gonadotropin (HP-hMG), follicle stimulating hormone (FSH), human chorionic gonadotropin (hCG). More information on medications will be provided in the next section.
4.1.2 Intrauterine insemination (IUI)
To shorten the pathway for the sperm to reach the egg and to increase the concentration of live sperm, the husband’s semen can be place inside the wife’s uterus directly. After hormonal stimulation in woman or a natural cycle, the husband provides a semen sample on the day of the wife’s ovulation. The active sperms will be selected in a laboratory (this procedure is called “semen washing”) and then place inside the uterus via a fine catheter. This procedure is a simple and safe. However, couples using IUI must have at least one patent fallopian tube and the husband’s semen should reach a satisfactory quality.
4.1.3 In Vitro Fertilization-Embryo Transfer (IVF-ET)
In IVF-ET, eggs are fertilized with the husband’s sperms outside the uterus and the fertilized embryo will be placed back to the uterus for implantation. It is suitable for couples with abnormal sperm or a very low sperm count, tubal disease, advanced age or patients who have failed after a few cycles of IUI.
18.104.22.168 Ovarian downregulation
Ovarian downregulation is usually the first step of IVF-ET prior to ovarian stimulation. This procedure uses medications to suppress your pituitary gland to prevent premature ovulation and synchronize the follicles sizes at the begining of the stimulation cycle, optimizing ovarian stimulation and having a better control over the entire process.
Depending on long or short (no down regulation) protocol is being used, the choice of medications and period of administration may vary. The commonly used medications are GnRH agonist, GnRH antagonist and contraceptive pill.
22.214.171.124 Ovarian stimulation
For a long protocol, daily injections of ovarian stimulating hormones will be started once the ovarian suppression is achieved. Multiple eggs will be stimulated during the procedure.
The pituitary having been surpressed, the functional Gonadotropins (FSH and LH) not being secreted as it would be in normal situation. Therefore and exogenous source is required and most of the medication regimes include drugs with FSH with or without LH activity.
Women will have ultrasound scan frequently to monitor the follicle growth and to consider the correct time for egg retrieval. Once there are enough eggs with an optimal size (usually around 18mm), hCG will be injected to trigger ovulation.
126.96.36.199 Egg retrieval
This procedure takes place in a hospital or a laboratory as suggested by your doctors. It involves inserting a narrow needle into the ovaries through the vagina under the ultrasound guidance. Follicles will be collected using the needle and being examined for the presence of eggs under microscope.
It is a relatively safe procedure and it will be done under anesthetic. The whole process usually takes only 15 to 30 minutes. You will stay for rest until you are recovered from anesthetic and it is suggested that you should have a companion with you upon discharge.
On the day, before egg retrieval, semen sample has to be collected and the sperm with the best quality will be selected through a procedure called “semen washing”. Eggs and sperm will be placed inside an incubator for fertilization. The cultured egg will be examined under microscope to check for fertilization on the day following egg retrieval.
188.8.131.52 Embryo transfer
If fertilization does occur and if good quality embryos exist, the embryos will be transferred back to the uterus between 3-5 days. This procedure requires no anesthetic or analgesia. The doctors will use an abdominal ultrasound to guide the process for placing the embryo at optimal position.
Normally, between 1- 3 embryos will be transferred in a single IVF cycle. The actual number of embryos being transferred depends on various factors, such as, the number and quality of the available embryos, the quality of the embryos, any previous unsuccessful attempts and the couple’s age. On deciding the number of embryos to be transferred, the chance of pregnancy and the risk of multiple pregnancy have to be balanced and taken into consideration, as the higher the order of multiple pregnancy, the greater the risk for pregnancy complications and long term morbidity to the unborn child.
The woman can return home after lying down for an hour or two. You will know the result in 10-12 days when pregnancy test can be performed.
184.108.40.206 Embryo freezing
If there are good quality embryos left after the first embryo transfer, you can consider whether to store the embryos. The embryos can be frozen for future use by cryopreservation.
220.127.116.11 Luteal support
In order to maintain your uterine lining (endometrium) to support implantation and the embryo development, progesterone or hCG supplementation is usually necessary after embryo transfer.
4.1.4 Intracytoplasmic Sperm Injection (ICSI)
ICSI is a technique of injecting a single sperm into the egg for fertilizition. The fertilized embryos will then be placed back to the uterus as in conventional IVF. All other procedures in an ICSI treatment cycle are no different as to conventional IVF. This technique increases the chance of fertilization and is necessary for men with very low sperm count and low-quality sperm. Theoretically, one single sperm is enough for ICSI, while a sperm count of 10,000 is needed for IVF.
18.104.22.168 In-Vitro Maturation (IVM)
The immature eggs are retrieved in an earlier stage of the menstrual cycle in an IVM cycle. It involves the culture of immature eggs to maturity in-vitro. Patients being treated with IVM require no or minimal ovarian stimulating drugs. It is therefore especially suitable for PCOS patients and so as to reduce the risk of OHSS.
22.214.171.124 Assisted Hatching
Assisted hatching is a comparatively new method used in ART. It involves making a small hole or thinning of the zona pellucida (the protective layer of an embryo) and as a result facilitating the implantation.
This technique is appropriate for women with advanced age, poor egg quality and quantity or embryos with thick zona pellucida.
126.96.36.199 Natural Cycle IVF/Minimal Stimulation IVF
Medications for ovarian stimulation are necessary for typical IVF cycle. In natural cycle IVF/minimal stimulation IVF, the patients will receive no or minimal amount of medications. There is only 1 egg produced during a natural menstrual cycle, therefore, the chance of getting good quality embryo is reduced and so as the pregnancy rate per cycle.
4.2 Infertility Medications
4.2.1 Ovarian downregulation
To prevent premature ovulation and have a better control over the whole treatment cycle, medications can be used to suppress the normal female hormone (FSH and LH) release. Doctors may adopt what is known as the long protocol, in which GnRH agonist is administered prior to the start of ovarian stimulation. Whilst some doctors adopt the so called short protocol, in which injections of GnRH antagonist are administered after the start of ovarian stimulation. Sometimes, contraceptive pill is used together with GnRH agonist or antagonist to achieve ovarian downregulation.
4.2.2 Ovarian stimulation
Clomid and Gonadotropins are the common medications used for the stimulation of multiple eggs in ovary. Due to the suppression of FSH and LH, the choices of Gonadotropin often include drugs with FSH +/- LH activity. FSH is necessary for follicle stimulation and development, whilst LH is needed for egg maturation and endometrial preparation for implantation. FSH activity is commonly provided by highly-purified FSH or recombinant FSH, while LH activity can be provided by highly-purified hMG and recombinant LH. Highly –purified hMG is a kind of medication contains both FSH and LH activities.
4.2.3 Luteal Support
In normal situation, progesterone and hCG are produced by the women’s body if pregnancy occurs. Progesterone is required for preparing the endometrium before implantation and maintaining the endometrial thickness. hCG is needed for maintaining the nutrient supply of the endometrium after embryo implantation. Therefore, progesterone and/or hCG are supplemented for the women after embryo transfer during ART treatment. Progesterone can be administered by injection or vaginal tablet, while hCG is only available in injection. Luteal support may continue for 8-10 weeks after the confirmation of pregnancy.
4.3 Complications of IVF Treatment Cycle
4.3.1 Ovarian Hyperstimulation Syndrome (OHSS)
OHSS is a complication due to overstimulation of the ovaries leading to an exaggerated response. Occasionally, the ovaries may produce a large numbers of follicles (>20 to 30) in response to stimulation, this in turn leads to increased vascularisation around the ovaries which can be very swollen. The symptoms may be insignificant in mild form of OHSS, nevertheless, it is a serious complication if severe OHSS occurs and can potentially be fatal. Symptoms include fluid retention leading to swollen abdomen and retention of fluid in the lungs – in turn leading to difficulty with breathing. Urine output may also be decreased. Your doctor will keep an eye for any risk of severe OHSS development the incidence is about 1-4% of cases. You must consult your doctor if you experience any symptoms of OHSS.
Cancelling of stimulation cycle or embryo transfer may be necessary in some high risk cases. The chance of getting OHSS is higher in women with polycystic ovaries.
4.3.2 Risk of a multiple pregnancy
Multiple pregnancy is a common complication in women under ART treatment. The more the embryos transferred, the higher the possibility of getting a multiple pregnancy. There is a chance of 17% with twin pregnancy and 3% with triplet if 3 embryos are transferred. The risks of miscarriage, preterm labour, restricted fetal growth, pregnancy complications in mothers and the need for operative delivery are much higher in multiple pregnancy. A balance should be made between the pregnancy rate and the complications resulted from multiple pregnancy when considering the number of embryos transferred.
4.3.3 Risk of Ectopic Pregnancy
Ectopic pregnancy is a well-known complication in ART. It refers to the condition which the embryo is implanted somewhere else rather than in the uterus. The most common site of ectopic pregnancy is in the Fallopian tube, other less common sites are the ovary and cervix. The suggested incidence of ectopic pregnancy for women under ART treatment varies between 2% to 11%, which is much higher than in natural pregnancy.
4.3.4 Risk of egg collection procedure
In the procedure of egg collection, a needle is inserted through the vagina wall into the ovaries under ultrasound guidance. The needle may penetrate the surrounding blood vessels or organs unintentionally. It may require operations or medications to correct the problems. The risk of this complication is extremely low and measures have been taken to reduce the risk by the clinicians.
4.1.1 誘發排卵 (OI)
4.1.2 宮腔內人工授精 (IUI)
當腦下垂體被抑壓，兩種功能性促性腺素 (FSH和LH) 就不會像正常週期般分泌出來。於是就需要一個外源來輔助，而大部份藥物都含有FSH活性，而LH活性就視乎不同藥物而定。
一般來說，每次體外受精(IVF) 週期會移植1- 3個胚胎。移植胚胎的實際數目取決於各種因素，包括：可用胚胎的數量和品質、以前曾否移植失敗以及夫婦的年齡。在決定移植胚胎數量時必須慎重考慮，在懷孕率和多胎妊娠的風險之間取得平衡，因為胚胎數目愈多，出現懷孕併發症的風險和未出生孩子的長遠發病率就愈高。
188.8.131.52 自然週期體外受精（Natural Cycle IVF/Minimal Stimulation）
要刺激卵巢裡的多個卵子，排卵藥和促性腺素都是常用的藥物。由於FSH和LH分泌被抑壓，通常會選擇含有FSH活性的促性腺素，藥物裡也可能含有LH活性。FSH對刺激卵泡發育很重要，而LH 則有助卵子成熟及為子宮內膜作好胚胎著床的準備。FSH活性一般由高純度FSH(HP-FSH)或基因重組FSH提供，而LH活性則由高純度人絕經期促性腺素(HP-hMG)或基因重組 LH提供。HP-hMG是種同時包含FSH和LH活性的藥物。