Treatment for Infertility

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4.1. Treatment for infertility

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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.

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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)

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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)

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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.

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4.1.3.1 Ovarian downregulation

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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.

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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.

 

4.1.3.2 Ovarian stimulation

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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.

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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.  

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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.

 

4.1.3.3 Egg retrieval

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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.

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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.

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4.1.3.4 Fertilization

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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.

 

4.1.3.5 Embryo transfer

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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.

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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.

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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.

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4.1.3.6 Embryo freezing

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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.

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4.1.3.6 Luteal support

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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)

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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.

 

4.1.5 Others

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4.1.5.1 In-Vitro Maturation (IVM)

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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.

 

 4.1.5.2 Assisted Hatching

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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.

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 4.1.5.3 Natural Cycle IVF/Minimal Stimulation IVF

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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

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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

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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

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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

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4.3.1 Ovarian Hyperstimulation Syndrome (OHSS)

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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.

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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

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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

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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

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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.   

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治療

 

4.1 治療方法

 

4.1.1 誘發排卵 (OI)

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對很多夫婦來說，簡單的治療或與輔助生育技術(ART)同樣有效。比方說，配合排卵時間行房可以提高懷孕率。

誘發排卵治療可進一步提高懷孕機會，做法是在配合排卵時間行房之餘，同時服食治療不育的藥物。這些藥物分口服和注射兩種，可刺激卵子的生長和排出，例如：口服排卵藥（clomiphene citrate）、高純度人絕經期促性腺素(HP-hMG)、FSH和人類絨毛膜性腺激素(hCG，即排卵針)。下一章會介紹更多藥物資訊。

 

4.1.2 宮腔內人工授精 (IUI)

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為縮短精子會合卵子的路程並提高活精子的濃度，丈夫的精液可直接放進妻子的子宮腔裡。在女性自然週期或接受荷爾蒙刺激後，丈夫須於妻子的排卵日提供精液樣本。活躍的精子會獲選送往實驗室（此程序稱為「洗精」），然後經由一幼小膠管注入子宮內，過程簡單安全。不過，採用IUI療程的夫婦，妻子必須擁有至少一條暢通的輸卵管，而丈夫的精液質量亦須達一定水平。

 

4.1.3 體外受精(IVF-ET)

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在體外受精的過程中，卵子在子宮外與丈夫的精子結合受精，然後受精的胚胎會被放回子宮腔內著床。此方法適合精子不正常或數目稀少的男士、輸卵管疾病患者、高齡產婦或接受過數週期宮腔內人工授精（IUI）治療失敗的人士採用。

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4.1.3.1 垂體降調節

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垂體降調節通常是體外受精(IVF-ET)的第一步，須在刺激排卵前進行。此程序使用藥物抑壓腦下垂體，防止過早排卵，並在刺激週期開始時統一卵泡大小，使排卵達至最佳效果，並有效控制整個排卵過程。

選用的藥物和用藥時間的長短，會因應醫生使用長方案或短方案而異。常用的抑壓卵巢藥物包括：GnRH 促效劑、GnRH拮抗劑和避孕藥。

 

4.1.3.2 刺激排卵

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以長方案來說，當卵巢成功被抑壓，就會開始每天注射刺激排卵的荷爾蒙。在此程序中，卵巢會被刺激，促進多顆卵泡成熟。

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。

女方須經常接受超聲波掃瞄，監察卵泡生長情況，以準確地決定取卵時間。當符合最適當大小的卵子(一般約為18毫米)達到足夠數量，女方便須注射人類絨毛膜促性腺素（hCG，俗稱「排卵針」），誘發排卵。

 

4.1.3.3 抽取卵子

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此程序會在醫院或研究室內進行，根據醫生的建議而定。做法是在超聲波的引導下，將窄小的採卵針經由陰道插入卵巢，抽取卵泡，拿到顯微鏡下觀察是否有卵子存在。

此手術相對較安全，會在麻醉下進行。整個過程一般只需15-30分鐘。你需要留院休息直至麻醉藥藥力散去，在此手術後，一般建議在親友陪同下出院。

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4.1.3.4 受精

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當天，在取卵之前，須先抽取精液樣本，進行一項名為「洗精」的程序。品質最好的精子會選出與卵子一同被放進培養皿內進行受精。取卵後一天，人員會用顯微鏡觀察接受培養的卵子，檢查它有否受精。

 

4.1.3.5 胚胎移植

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若有卵子受精而胚胎品質理想，在三至五天內，胚胎就會被移植回子宮裡，此程序無需使用麻醉藥或鎮痛劑。醫生會在腹部超聲波的引導下，將胚胎放置到最適當的位置。

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。

在胚胎移植完畢，女士趟臥休息一、兩小時後即可回家，10-12天後便可進行懷孕測試。

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4.1.3.6 胚胎冷凍

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在首次胚胎移植後，若有品質好的胚胎剩餘，你可以考慮將胚胎冷凍儲存。

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4.1.3.6 黃體支持

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胚胎移植後，為確保你子宮內膜的情況足以支援胚胎著床及發育，通常須要使用補充黃體酮或人類絨毛膜促性腺素 (hCG)。

 

4.1.4 單精子卵漿內注射(ICSI)

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單精子卵漿內注射技術(ICSI)，是將單一精子直接注射入卵子內達至受精。跟傳統體外受精（IVF）一樣，受精的胚胎會被放回子宮內。ICSI療程中的其他程序也與IVF無異。此技術可提高受精的機會，可以對精子數目稀少或品質低的男性有幫助。理論上， 一條精子便足夠進行ICSI，而IVF卻需要一萬條精子。

 

4.1.5 其他

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4.1.5.1 不成熟卵子體外培養(IVM)

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不成熟卵子體外培養療程（IVM）會在月經週期較早階段抽取未成熟卵子，將它在體外培養至成熟。接受IVM治療的病人只須服用最少量的刺激排卵藥物，甚至無須使用。 因此，此技術特別適合多嚢卵巢症候群（PCOS）病人採用，以減低患上卵巢過度刺激症（OHSS）的風險。

 

4.1.5.2 輔助孵化

輔助孵化技術是一種較新的輔助生育技術（ART）。做法是利用激光在胚胎的外膜上鑽一個小孔或將它磨薄，幫助著床。

此技術適合高齡、卵子稀少或品質差及胚胎外膜較厚的女士採用。

 

4.1.5.3 自然週期體外受精（Natural Cycle IVF/Minimal Stimulation）

在使用傳統體外受精(IVF)技術，病人必須服用刺激排卵藥物。而在自然週期體外受精過程中，病人只須服用少量藥物，甚至無須服用。 由於一次自然月經週期中只會產生一顆卵子，採用此技術而得到好品質胚胎的機會會下降，週期懷孕率亦會相應下降。 

 

4.2 不育藥物

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4.2.1垂體降調節

 

為防止過早排卵及更有效控制整個治療週期，病人可服藥抑壓正常的女性荷爾蒙（FSH和LH）分泌。醫生可能會採用長方案，在開始刺激排卵前注射促性腺釋放激素（GnRH）促效劑；他也可能會採用短方案，在開始刺激排卵後注射促性腺釋放激素（GnRH）拮抗劑。有時為令卵巢降調節成功，促性腺釋放激素（GnRH）促效劑及拮抗劑會配合避孕藥一同使用。

 

4.2.2 刺激排卵

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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。

 

4.2.3 黃體支持

在正常情況下，女性懷孕時會製造黃體酮和人類絨毛膜促性腺素（hCG）。黃體酮的作用是為子宮內膜保持厚度和作好著床的準備；hCG則會在胚胎著床後維持子宮內膜的養份供應。因此在輔助生育技術（ART）治療期間，胚胎移植後，孕婦需要補充黃體酮或hCG。黃體酮可以用打針注射或服用塞陰藥來補充，而hCG則只能打針注射。證實懷孕後，黃體支持或需持續8-10個星期。

 

4.3 體外受精治療可能出現的併發症

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4.3.1卵巢過度刺激症候群(OHSS)

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卵巢過度刺激症候群(OHSS)是一種因卵巢受到過度刺激而引起嚴重反應的併發症。當卵巢受到刺激，有時會製造出大量卵泡（20-30個)，繼而令卵巢周圍血管化，變得非常腫脹。若病情輕微，症狀或許不明顯；但若病情嚴重，OHSS可以是很嚴重的併發症，足以致命。症狀包括腹部積水引致腹脹及肺部積水，繼而令呼吸困難，排尿亦可能會減少。患上嚴重OHSS的機會率是1-4%，你的醫生會密切監察。若你察覺到任何OHSS症狀，請立即求醫。

在某些高風險個案中，或須終止刺激週期和胚胎移植療程。多嚢卵巢症候群患者有較大機會患上OHSS。

 

4.3.2 多胎妊娠風險

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多胎妊娠風險是輔助生育技術（ART）治療的常見併發症。移植胚胎的數量愈多，多胎妊娠的機會就愈大。你若接受三個移植胚胎，懷雙胞胎的機會是17%，懷三胞胎的機會則是3%。若出現多胎妊娠，流產、早產和胎兒發育受阻礙的風險會高很多，很多時候會需要剖腹取嬰，孕婦亦較易出現懷孕併發症。 因此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引起的併發症之間取得平衡。

 

4.3.3 宮外孕

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宮外孕是輔助生育技術（ART）最為人認識的併發症，是指胚胎在子宮以外的地方著床之現象。 宮外孕最常見的著床地點是輸卵管，其次是卵巢和子宮頸。接受ART治療的女士患上宮外孕的機會率介乎2-11%不等，比自然懷孕高出很多。

 

4.3.4 取卵手術的風險

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取卵手術進行時，醫生會在超聲波引導下將採卵針經由陰道壁插入卵巢，期間可能會不慎插穿附近的血管和器官，或需動手術或服藥治理。不過這意外出現的機會極低，醫生會做足預防措施避免此意外發生。