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Dr   W.A Helaruwan Pasan Kumara

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Follicular Tracking

Procedure; Normally a woman produces and releases one egg every month. If she has 28 to 30 day cycle, ovulation (release of egg from the ovary) occurs between day 12 to 16 of the cycle. In follicular tracking method, an ultrasound scan is arranged on day 10 of the cycle (day 1 is the first day of period). This scan will show the size of the follicle and the thickness and nature of the endometrium.

When the follicle reaches a size of 16 mm in diameter, one will be advised to use ovulation prediction kit (LH surge kit) which is available with any chemist. At the same time further scans will be arranged till the follicle reaches the size of 18 mm. When the ovulation prediction kit is positive (by showing 2 lines, it indicates the occurrence of LH surge to stimulate ovulation. The couple are then advised to have intercourse for the next three days starting from that day.

Who will benefit from this treatment? Women who have regular menstrual cycle (those who ovulate regularly). Women with unexplained infertility of a short duration (less than 2 years). Women under 30 years of age. Advantages This is the simplest form of assisted conception. There is no drug treatment. There is no risk of multiple pregnancy (as there is no stimulation of ovaries). Inexpensive treatment. Disadvantages The pregnancy rate is rather low (less than 10%). One has to be patient as it might take a long time to conceive by this method.

Intra-Uterine Insemination (IUI) Introduction Intra-Uterine Insemination (IUI) is commonly known as artificial insemination. This has been in use for over 100 years. Artificial insemination includes intra-vaginal, intra-cervical and intra-uterine insemination. The first two procedures were used in the past, but IUI is the most commonly used procedure nowadays. IUI can be performed with the partner’s sperm or donor sperm. Regarding the use of donor sperm, please refer to the sperm donation section. Procedure IUI is a very simple technique whereby washed sperm is deposited into the uterine cavity around the time of ovulation. This can be performed in a natural cycle or a stimulated cycle. The ovaries can be stimulated with Clomiphene Citrate alone or Clomiphene Citrate and Gonadotrophins (FSH injections) combination. The dose of Clomiphene (Clomid) tablet is usually 50-100 mg daily from day two to day six of the cycle and the dose of FSH injection is 50-150 IU on alternate days starting from the second day. Monitoring of the cycle is done by serial ultrasound scanning from day nine/day ten of the cycle. When there are two to three follicles of at least 18 mm in diameter, the trigger injection of 5000 IU of human Chorionic Gonadotrophin (HCG) is administered. IUI is usually carried out 24 hours after the injection. In some cases two inseminations are performed on consecutive days if the patients request it. The logic behind IUI treatment is threefold: 1. More than one egg is available thereby increasing the chance of success 2. Sperm are directly placed in the uterine cavity thereby reducing the destruction of sperm by the vaginal acidity and cervical hostility 3. It also reduces the distance the sperm have to travel to meet the egg in the fallopian tube Who will benefit from this treatment? Couple with unexplained infertility Women with mild endometriosis but with open tubes Couple with infertility due to a mild male factor Women with cervical hostility In couples where full penetrative intercourse in not feasible When men are unable to ejaculate inside the partner’s vagina The success rate is usually around 15-20%. Success rate, of course, varies with the age of the woman, and cause of infertility, as shown in the figure below.

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Advantages compared to IVF

  • Less invasive
  • Less emotional commitment
  • Less expensive
  • Less time consuming


  • Disadvantages compared to IVF

  • Fertilization is not confirmed
  • Woman must have open tubes
  • Risk of ovarian hyper-stimulation syndrome
  • Risk of multiple pregnancies


  • In Vitro Fertilization (IVF) Procedure

    What is involved in IVF treatment? The main strategy in IVF treatment is to stimulate the ovaries with hormones to produce multiple follicles containing eggs. These eggs are retrieved and mixed with sperm and embryos are generated.

    Ovarian stimulation

    The first step is the shutting down of the pituitary-ovarian hormones called down regulation. This is done with a drug known as Gonadotrophin releasing hormone agonist (GnRHa). This is available in the form of a nasal spray, daily subcutaneous injections or depot injections (the effect of one injection lasts for 4-6 weeks). This suppression can be started on day two or day 21 of a period depending on the type of protocol (long or short). Please see protocols. It takes approximately two weeks for complete suppression. This is confirmed by an ultrasound scan which will show a thin uterine lining and quiescent ovaries without any cyst. A blood test is also performed to check the hormonal level (Oestradiol) for the confirmation of down regulation or suppression. Once down regulation is confirmed the daily injections of FSH or menotrophin will be started to stimulate the ovaries. These injections need to be administered daily for 12-16 days. The GnRH agonist is also continued during this period of ovarian stimulation. Monitoring the cycle The ovarian response to the stimulation is monitored by serial ultrasound scanning and blood test. Usually, three to four scans are necessary during this two week period of injections. In addition, blood tests are carried out to check the level of Oestradiol along with scans in all patients. The scans are usually internal scans which give a better picture of the uterus and the ovaries. During the scans the number and the size of the follicles are measured and the thickness and the texture of the lining of the womb are assessed. When the leading follicles reach a diameter of 18 mm or over, the lining of the womb is at least 8 mm in thickness and the Oestradiol levels correspond to the number of growing follicles, it is time to give the trigger injection (HCG injection). At this stage, the GnRH agonist and FSH or menotrophin injections will be stopped. The trigger injection is the Human Chorionic Gonadotrophin (HCG) which starts the maturation process of the eggs. This is usually given in the late evening and the egg collection will be performed 36 hours later. Natural cycle IVF This term refers to IVF treatment using one’s natural cycle i.e. without any stimulation with drugs. Normally, only one egg is produced and released every month. This egg is collected and mixed with sperm. If fertilization takes place, there is one embryo which is replaced after 48 hours. The main advantage is that there is no injection or use of any other drugs. This means there are no side effects of drugs. Usually, the injections used in the treatment of IVF are expensive. Hence, natural cycle IVF is also cheaper. The main disadvantage is that the chance of success is rather low because there is only one egg and one embryo.

    Egg collection procedure

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    Egg collection is usually performed in the morning, approximately 36 hours after the HCG injection.

    Route: the egg collection is performed vaginally under ultrasound guidance. When IVF was started the egg collection was routinely done laparoscopically. Because of the invasive nature of this method, it is used only in selected cases. For example, if one or both ovaries are not accessible vaginally, laparoscopic egg collection is performed.

    Anaesthesia: the vaginal egg collection is done under intravenous sedation (conscious sedation). Some centres use general anaesthesia for this procedure.

    Procedure: a needle is attached to the vaginal probe of the ultrasound. Under ultrasound guidance, the needle is passed through vagina and into the ovary, as shown in the diagram above. The fluid from an ovarian follicle is aspirated and the fluid is passed to the embryologist who identifies the egg in this fluid under a microscope. If there is no egg, in the aspirated fluid the follicle is flushed with culture medium and sucked out. Once the egg is identified, the needle is moved to the next follicle and the procedure is repeated. Once all the follicles are emptied, the needle is taken out of the ovary and passed into the other ovary and the same procedure is carried out.

    The number of follicles does not correspond to the number of eggs collected. Some follicles may not contain an egg. After the procedure Transvaginal egg collection is a relatively safe procedure. It takes an average of 20-30 minutes. The woman is allowed to go home after two hours. She must be taken home by her partner or friend. She should not drive a vehicle for 24 hours. After the egg collection procedure, there may be some discomfort or soreness in the tummy. This might be more if the number of eggs collected is more (more than 12). Pain-killers can be used to control the symptom. This will not interfere with the fertility treatment. There may be some spotting. This is usually minimal and dark brown in colour. This may be due to the oozing from the needle puncture site in the vagina. There may be nausea and vomiting. This can be due to the anaesthetic drugs or mild hyper-stimulation. When the number of eggs is more than 15, there may the bloating of the abdomen. If any of the symptoms becomes severe, one should consult the doctor.

    Semen sample

    The husband or the patient’s partner is required to produce a semen sample on the day of egg collection. The man is advised to abstain for 2-3 days prior to producing sample. If the period of abstinence is more than 7-10 days, the quality of the semen sample may become poor. The semen sample is generally produced by masturbation. It is recommended that the man washes his hands and genitals with soap, rinses with clean water and dries with a clean towel. No lubricant such as petroleum jelly, should be used during masturbation to avoid problems of toxicity to sperms. The sample is collected into sterile plastic containers which are non-toxic to the sperm. The partner usually produces the sample in a separate room in the clinic. This is to ensure that the sample is as fresh as possible. If some men find it difficult to produce samples in the clinic’s environment, they can produce sample at home and bring it to the clinic, provided it is delivered within one hour. Also, it is important to keep the sample warm by carrying it in the inner pocket of the jacket. If some men find it difficult to produce into a small plastic container, they can use a special condom provided by the clinic. This condom is a special one and does not have the spermicidal agents present in the normal condoms. If the partner is not going to be available on the day of egg collection, he could produce a sample before and have it frozen. The frozen sample can be thawed and used for the treatment. If a partner has or is likely to have difficulty in producing a sample, it is better for him to produce a sample before the commencement of the treatment and freeze it as a backup arrangement.

    Progesterone supplementation

    After the egg collection, the patient is advised to take the hormone progesterone as a support for the implantation. This is usually given in the form of a pessary or suppository. It is given in the dose of 400 mg twice daily rectally until embryo transfer and rectally or vaginally after embryo transfer. This is continued until the day of pregnancy test which is performed 12 days from the embryo transfer. In the pleasant event of the test being positive, it is continued for another two months (till 12 weeks of gestation). If the pregnancy test is negative, the medication is stopped on that day.

    Fertilization

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    The eggs and the prepared sperm are mixed in a cultured medium in the laboratory. This is kept in a labelled dish in an incubator. The dish is checked next morning for fertilization. The sign of fertilization is the presence of two pronuclei (one from the sperm and one from the egg), as shown in the picture on the right. Normally about 60% of the eggs fertilise. The embryos are checked for further cell division the next day. There should be 2-4 cells the next day (day 2) and 6-8 cells on the third day, as shown in the pictures on the right. Sometimes the embryos may be rather slow in their division. The embryos which have divided and show regular outline and minimal or no fragments are usually transferred. The grading of the embryos is based on the regularity of cellular outline and the presence of fragment. The number of embryos to be transferred will be discussed with the patient/couple. In general, it is recommended to have one embryo transferred if the patient is under 35years of age. This is to reduce the risk of twin pregnancy. In the UK, the HFEA allows clinics to transfer a maximum of two embryos in women under the age of 40 years and 3 embryos in women of 40 years and above. Depending on the number of embryos available, after choosing the best embryo for transfer, the other embryos will be frozen for future use if they are of good quality.

    Embryo transfer

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    The embryo transfer is a simple procedure. Normally no anaesthesia is used for this procedure. However, in some difficult cases, mild sedation may be used. The couple may be able to see the embryos through a monitor before the procedure.

    Procedure: The woman lies on the couch with her legs in stirrups. The doctor introduces a speculum to visualise the cervix and then cleans the cervix. Meanwhile, the embryos are loaded on to a catheter by the embryologist. Finally, the doctor introduces the catheter gently into the uterine cavity and deposits the embryos. Embryo transfer is carried out under ultrasound guidance with a full bladder. This is to visualise the position of the catheter and the placement of the embryos. This is reassuring to the doctor and the patient. In addition the full bladder may correct the angle between the cervix and the body of the uterus and make the transfer easier. This is to reduce the trauma to the embryos during the procedure. After transferring the embryos, the catheter is withdrawn slowly and handed over to the embryologist. The embryologist checks the catheter to make sure that no embryo is left in the catheter. If one or more embryos are retained in the catheter, they are loaded again and replaced. This does not reduce the chance of success. If the transfer is difficult, a tenaculum is applied to the cervix and a different catheter which would negotiate the angle between the cervix and the uterus is used. After the embryo transfer, the patient is advised to lie down for 15 minutes. She is then allowed to get up and empty her bladder. The question that is present in every patients mind: “Will the embryos fall out when I get up?” Luckily, the answer is: no.

    Dos and don’ts after embryo transfer: Take it easy for the next few days. This does not mean bed rest. One can take leisurely walks. It is better to avoid strenuous activities, lifting heavy weights, jogging, riding and gym activities. Avoid swimming.

    Pregnancy test

    During IVF treatment, a blood test is performed 14 days after the egg collection. This period of waiting is very stressful for couples. This is said to be the longest two weeks in one’s life. There is nothing one can do to improve the chances. The pregnancy test is a quick test and the result should be ready in one or two hours. If the test is positive it is usually repeated within 2-5days to check the rising level of the hormone β-HCG. If the hormone level does not rise in the usual pattern, it indicates problems with the pregnancy, such as miscarriage or ectopic pregnancy. This is followed up with serial blood test. Some women may start spotting or bleeding before the pregnancy test is due. They may assume that they have started period and not attend the hospital for the blood test. It is important that a blood test is carried out even under these circumstances to establish whether there is a pregnancy or not. Positive outcome: if the pregnancy test is positive, the woman is advised to continue with the progesterone supplementation. An ultrasound scan is arranged 2-3 weeks after the test. This is to confirm that the pregnancy is in the right place (uterus), check the number of pregnancy sacs and viability of foetuses. If the findings are normal the progesterone is continued for another 5-6 weeks (until 12 weeks of pregnancy). Negative outcome: this is the worst fear of every woman who goes through IVF treatment. If the pregnancy test is negative, the progesterone supplementation is stopped. The negative pregnancy test is very upsetting to the couple. Some couples may benefit from seeing a counsellor. They need time to recover from the shock. When they are in a position to discuss the matter they can make an appointment to see the doctor in hospital/clinic to plan for future treatment.

    Complications

    Ovarian hyperstimulation syndrome (OHSS)

    This is one of the most important complications of IVF treatment. The ovarian response to stimulation may be excessive with the ovaries becoming enlarged and fluid accumulation in the abdominal cavity. This can be mild, moderate or severe. Mild: this occurs in some 10-20% of the cases. The usual symptoms are abdominal distension and discomfort, nausea, vomiting, and diarrhoea. Ultrasound scans shows ovarian enlargement of less than 5 cms. Moderate: this occurs in some 5% of the cases. The usual symptoms are as described for mild OHSS. Ultrasound scan shows accumulation of fluid in the abdominal cavity and ovarian enlargement between 5-12 cms. Severe: this occurs in some 1-2 % of the cases. The ovarian enlargement is over 12 cms. There is breathing difficulty and clinical ascites. Other features like haemoconcentration, coagulation disorders, oliguria and liver and renal failure may be present.

    Treatment

    Mild: all that is needed for mild OHSS is an ultrasound scan to confirm the diagnosis and for reassurance. Bed rest, increased intake of oral fluids and mild analgesics such as Paracetamol are helpful.

    Moderate: patients with moderate OHSS need close monitoring with ultrasound scans, blood tests and intravenous fluids if necessary.

    Severe: severe cases of OHSS may require hospital admission. Drainage of the fluid in the abdomen by vaginal route under ultrasound guidance will relieve some of the symptoms markedly and help the patients recover dramatically.

    Multiple pregnancy

    The incidence of multiple pregnancy is high as more than one embryo is transferred to improve the chance of success. If 100 women conceive after three embryo transfers 75 of them will have singleton and 25 twins. These figures represent approximately 20 and 50 times increased frequency for twins compared with spontaneous conception. These twins are non-identical (different eggs)twins. Sometimes, the single embryo may split and give rise to identical twins (monozygotic twins). This is the reason why a patient who has only one embryo transferred can still have twins and the woman who has two transferred can have triplets. This risk is particularly higher with blastocyst transfer and assisted hatching. The incidence of monozygotic twins is 4.9% of IVF treatment, 12 times higher than the 0.4% rate observed in natural conception. With multiple pregnancy, the pregnancy is more complicated than singleton pregnancy. The risk to the mother is increased due to complications of pregnancy such as pre-eclampsia, diabetes, placenta praevia and postpartum haemorrhage. The babies have an increased risk due to pre-term labour, intra-uterine growth restrictions and malformations. The perinatal mortality rate is higher in twins compared to singleton pregnancies.

    Ectopic pregnancy

    This is more common after IVF treatment than in the general population. The incidence is 3-5% after IVF treatment. When a woman has high risk factor for ectopic pregnancy, such as previous ectopic, damaged tubes, previous tubal surgery and past history of PID, serial measurements of quantitative β-HCG is carried out. If the β-HCG does not rise in the usual way, an early ultrasound scan is arranged to exclude ectopic pregnancy. Laparoscopy may be needed to exclude ectopic pregnancy if there is no gestational sac seen in the scan.

    Heterotopic pregnancy

    This refers to a combination of intrauterine and extra uterine pregnancy. This is rare in spontaneous conception with an incidence of 1 in 20,000 to 30,000; but it increases dramatically after IVF treatment.

    Miscarriage

    There is a 20-25% risk of miscarriage with IVF treatment. The risk of miscarriage with spontaneous conception is 15%. The higher incidence of miscarriage in IVF may be due to polycystic ovaries in these women. Risk of ovarian cancer following ovarian stimulation A lot of research has been carried out to study the association between the ovarian stimulation and ovarian cancer. So far, no increased risk has been observed.

    Protocols

    Protocols for ovarian stimulation in IVF treatment There are different protocols for ovarian stimulation. In the initial days of IVF treatment, there was no hormonal suppression as the drug GnRH agonist was not available. Clomiphene citrate tablets and Gonadotrophin injections were used for ovarian stimulation for approximately 12-14 days and when the follicles reached the mature size (>=18 mm), the egg collection was planned. With the introduction of GnRH agonists, other protocols emerged.

    Long

    Long Luteal: this is the standard protocol and is used when the woman has regular 28-30 day cycle. The hormonal suppression (down regulation) is commenced on day 21 of the period before treatment. It can be in the form of daily subcutaneous injection, nasal spray or a single injection of depot preparation (the effect of which lasts for 4-6 weeks). The next period usually starts 7-10 days after the commencement of the spray or injection. After confirmation of down regulation with an ultrasound scan and blood test on day 5 of the period, the FSH injections are started to stimulate the ovaries. These injections are administered daily by the subcutaneous route for approximately 12-16 days till the leading follicles reach the size of >= 18 mm, when the egg collection is planned. At this stage, the suppression spray or injection is stopped and a trigger injection of Human Chorionic Gonadotrophin (HCG) is administered 36 hours before egg collection.

    Pill: this protocol is used in women with long or irregular cycles. The purpose of the pill is to regulate the cycle. It is started on day 1 or 2 of the period. The downregulation is commenced on day 17 of the pill. The course of pill will finish on day 21 which will be followed by a period after a few days.The rest of the steps are the same as above.

    GnRH antagonist protocol

    As GnRH inhibits the premature LH surge selectively, there is no need for the down regulation of all the hormones with this protocol. This is a “soft stimulation” protocol as the number of days of FSH injections and the number of ampoules needed is lower, thereby reducing the cost. Therefore it is a “patient friendly” protocol. The main advantage of this protocol is to reduce the risk of OHSS in women with polycystic ovaries. Poor responders produce more eggs with this protocol. The stimulation starts on day 2 of the period with FSH or HMG injections. This is started after a baseline check scan. In women with previously raised FSH or poor response hormone levels are checked before commencing treatment. Serial scans are performed from day 6 onwards. GnRH antagonist (Orgalutran, Cetrorelix or Antagon) injection is started on day 6 and administered daily in the form of a subcutaneous injection till the day of HCG injection. The patient will be having 2 injections daily (FSH and GnRH antagonist injection).

    Advantages of treatment

    Advantages of IVF

    Key information about fertilization between sperm and egg is obtained only in IVF treatment One can assess egg and embryo quality Surplus embryos can be frozen

    Success rate with IVF treatment

    This varies from country to country (due to varying restrictions in different countries) and in the same country, from one clinic to another. The clinical pregnancy rate varies from 30-50%. The presence of intra-uterine gestation with foetal heart movement is defined as clinical pregnancy. Some of these pregnancies end in miscarriages. The live birth rate or “take home baby rate” varies from 25-40%.

    Factors affecting the success rate

    Age of the woman: this is the most important factor affecting the success rate with assisted conception treatment. The younger the woman, the higher is the success rate. The success rate declines considerably in women over the age of 40 years. Duration of infertility: there is some evidence to say that the longer the duration of infertility, the lower the success rate with IVF treatment. Type of infertility: women who have had children or who have been pregnant in the past do better with IVF treatment. Those who have had a baby from previous IVF treatment have a higher chance of success. Cause of infertility: women with tubal factor, particularly hydrosalpinx have a reduced chance of success compared to other female causes of infertility. Couples with male factor infertility that is treated by intra-cytoplasmic sperm injection (ICSI) have a higher chance of success. Number of previous IVF treatments: live birth rate is highest in the first cycle and it becomes lower after three attempts. The cumulative pregnancy rate after three attempts of IVF is in the region of 70-80% which is encouraging. Not everybody is lucky to become pregnant in the first attempt. The important thing is to keep trying. Quality of embryos: this is one of the important criteria for success. The higher the quality of embryos, the better is the chance of success. The quality of embryos depend on the quality of eggs which is related to female age, and quality of sperm. This is the reason for higher success rate with egg donation programme where the eggs are obtained from young and fertile women. Number of embryos transferred: transferring a higher number of embryos leads to a greater chance of success. However, this is associated with a higher risk of multiple pregnancy. But according to HFEA regulations, only one or two embryos are allowed to be transferred in women under the age of 40 years; women aged 40 and above are allowed to have up to 3 embryos. Younger women (under 35 years) are advised to have single embryo transferred if their embryo grade is excellent, to reduce the risk of twin pregnancy.

    Additional procedures

    Assisted hatching

    Introduction

    The shell or protective layer of the embryo is called zona pellucida. This may become hard due to the laboratory techniques involved in IVF and due to freezing techniques. The assisted hatching procedure involves thinning or making a hole in the zona pellucida to help the hatching process of the embryos. There is some evidence that assisted hatching might improve the implantation rate.

    Techniques

    A hole can be made in the zona by a micro-needle or with the use of a chemical called acid Tyrode’s solution or with a laser. Of these, the laser technique is the best as it has a greater degree of control and more precision during the procedure. A laser can be used to create a full thickness breach or thinning of zona pellucida. Assisted hatching is performed immediately prior to transferring the embryos into the womb.

    Effect on treatment outcome

    Some studies have reported improvement in the outcome following assisted hatching. However, some clinicians have reported no difference in outcome.

    Who will benefit from assisted hatching?

  • Women older than 38 years
  • Women with repeated unsuccessful treatments with IVF
  • Women with high FSHEmbryos with a thick zona pellucidaEmbryos that have been frozen and thawed

    Risks

    Assisted hatching increases the risk of monozygotic twinning.

    Blastocyst transfer

    Introduction

    This is a new technique developed to maximise the chance of success with IVF treatment. For IVF treatment, the embryos are normally replaced on the second or third day of fertilization, but in blastocyst transfer they are replaced on the fifth day.

    Technique

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    With this technique, the embryos are kept in the culture medium in the laboratory till the fifth day of fertilization. A day 2-3 embryo has 4-8 cells whereas blastocyst, or day 5 embryo, has more than 100 cells. It has differentiated into thin outer layers of cells which will develop into placenta and an inner cell mass which will develop into the foetus. There is a cavity inside and hence the name blastocyst, as shown in the picture. The metabolic requirement of the embryos changes after the third day and therefore they have to be placed in different culture media, which is called sequential media for this technique.

    How does it work?

    Usually one has to have 8-10 embryos on the day of fertilization. Everyday the scientist will look at the embryos to see how many of them have divided and place them in sequential media. Some embryos may stop dividing and on the third day there may be only six embryos which have divided. Out of the six embryos only three or four may develop into blastocysts. Others may not have divided. If one started with eight embryos on the first day, and by the third day, if there are less than four embryos, it is better to have these embryos replaced on that day rather than continue with the original plan of blastocyst transfer. As far as the transfer procedure is concerned, it is the same as the conventional day two or day three embryo transfer. As the implantation rate is high with blastocysts it is advisable to have only one or two blastocysts for transfer to avoid multiple births. Supernumerary blastocysts can be frozen for future use. Blastocyst transfer can be used with frozen-thawed embryo transfer treatment also. A minimum of at least eight embryos should be in storage for this. All of them can be thawed and embryos transferred at blastocyst stage.

    Who will benefit from blastocyst transfer?

    Women who have had two or more failed IVF attempts following the transfer of good quality embryos and who produce good number of eggs.

    Women who would like to avoid multiple pregnancy without reducing their chances.

    Women who do not wish to have the surplus embryos frozen for whatever reason may benefit from this technique.

    Advantages

    This technique gives the clinicians the opportunity to choose the best embryos for the transfer. If embryo has divided and developed into blastocyst stage, it is more likely to continue to grow and get implanted. With day 2-3 transfers, the embryos may stop growing inside after transfer. In a natural cycle, this is the stage at which the embryo reaches the uterine cavity. The uterine endometrium is said to be more receptive on day 5 rather than on day 2-3 and quiescent without any substantial myometrial contractions. All of these contribute to a success rate of 50-60% with blastocyst transfer in IVF treatment.

    Disadvantages

    The risk of monozygotic twins is higher.

    Intra-Cytoplasmic Sperm Injection (ICSI)

    Procedure

    After the egg collection, the cumulus cells, which surround the egg, are removed. This is called stripping the egg for ICSI. A healthy and active sperm is selected and rendered immotile. It is then sucked into the tip of a very fine glass needle (tail first) and injected into the egg (head first). The egg is held in place using a pipette. The injection is a delicate procedure and involves the use of a micro-manipulator (an instrument used to carry out ICSI under the microscope). A small percentage of eggs, roughly 5%, may be damaged by this procedure.

    Who will benefit from ICSI?

  • When the sperm concentration is less than 10 million per ml.
  • When the motility of the sperm is less than 30%.
  • When there are a high number of abnormal forms – more than 90%.
  • When there are antibodies in the semen as indicated by a significantly positive MAR test result of more than 90%.
  • Previous failure of fertilization or a fertilization rate of less than 20% with conventional IVF.
  • When sperm is retrieved by PESA/TESA procedure.
  • IVF+ICSI split combination treatment


  • Sometimes IVF and ICSI can be combined in the same treatment cycle. Half the number of eggs could be subjected to IVF treatment (inseminated with sperm) and the remaining eggs could be used for ICSI treatment (where sperm is injected into the eggs). This combination will be very useful when the sperm parameters are border-line. For example, if the sperm count is between 10-20 million and the motility is between 30-50%, half IVF and half ICSI can be done. Or, if the male partner has had a borderline sperm count or motility in the past, but on the day of egg collection, the sperm count, motility and preparation are normal then one could consider half IVF and half ICSI. However, for this combined treatment, one should have a minimum of at least 12 eggs. Sometimes this is used in couples with unexplained infertility. This technique gives the best of both the treatments. If one has ICSI to be on the safe side, then ICSI has to be repeated again, if the treatment is not successful, without knowing whether it is really necessary or not. If on the other hand, one has IVF, there is a risk of failure to fertilise. This means that there are no embryos for transfer and the whole treatment would have been wasted. Risks ICSI is an invasive technique and so patients are understandably concerned about abnormalities that may result in a child conceived through this procedure. The risk of having congenital (birth) abnormality following ICSI treatment is the same as for IVF and in the general population. However, the risk of chromosomal anomalies particularly the sex chromosomal anomalies is increased (0.08% versus 0.3%). There is also a risk of transmitting the fertility problem to the offspring. In view of the increased risk of sex chromosomal abnormalities in ICSI pregnancies, it is advisable to have a blood test to check the chromosomes of both partners. If any anomaly is detected, it will be advisable to seek genetic counselling. Men with no sperm in the ejaculate may have absence of vas deferens (this is the tube which transports sperm from the testis to the base of the penis). Such men are more likely to carry the cystic fibrosis gene mutation. It is advisable for such men to undergo a screening test for cystic fibrosis (which is a blood test) before embarking on fertility treatment.

    Advantages

    This is the only treatment for couples with very low sperm count or very low motility. This gives the couple an opportunity to have a baby with their own gametes.

    Success rate for ICSI

    The success rate depends on the skill and experience of the person performing the injection procedure, and so varies from place to place. Other factors such as the woman’s age, duration of infertility, quality of the embryos and number of embryos transferred also affect the success rate.

  • The fertilization rate with ICSI is 60% to 70% and complete failure of fertilization occurs in less than 5% of cases.
  • The clinical pregnancy rate is between 50% and 60%
  • The live birth rate is between 40% and 45%.
  • IVF with donor eggs

    Introduction

    Egg donation refers to a form of assisted conception treatment whereby another person’s eggs are used. The woman who donates eggs is the donor and the woman who receives the embryos (fertilized eggs) is the recipient. Unfortunately, some women and couples face a difficult situation in which their only chance of conceiving is with donated eggs. In many cases this is because the woman’s biological clock – the woman’s store of eggs in her ovaries has run out. Typically, this occurs as women reach their mid 40s, ahead of the menopause but it can also occur in younger women who have premature ovarian failure. The increasing demand for donor eggs Over the past two decades, the age at which women have their first baby has been increasing. Currently, the average age of first pregnancy for women in European countries is close to 30. One of the many consequences of this dramatic social change is a greater occurrence of age-related infertility. Many have simply left it too late to conceive naturally. Donor eggs are also needed for young women surviving cancer for whom cancer treatment has caused loss of ovarian function and for some women who are increased risk of passing along a genetic disorder. Hence, there is an ever increasing demand for egg donors. The increasing availability of donor eggs at HSFC Due to recent changes in the legislation by the Human Fertilisation and Embryology Authority (HFEA), the UK regulator of fertility and increasing awareness of the demand for donor eggs, our clinic has seen an increasing number of donors come forward. This has resulted in our waiting list for donor eggs being dramatically cut. We now expect to match most recipients with a suitable donor within 3 months even for patient of ethnic minority origins! Our donor egg bank was started due to the increased availability of egg donors: we often found ourselves unable to match an egg donor with a suitable recipient. Therefore, we freeze the eggs from such donors. This has only be made viable due to the new egg freezing techniques that provide over 90% survival rates for the freezing process.

    Who will benefit from egg donation?

  • Women whose ovarian reserve is low or nil
  • Women born without functioning ovaries (e.g. Turner syndrome)
  • Women who have their ovaries removed for cancer, ovarian tumour, or endometriosis
  • Women whose ovaries were damaged by previous chemotherapy or radiotherapy
  • Women who have recurrent IVF failures
  • Women who have inheritable conditions: sex linked diseases such ashaemophilia, Duchene’s muscular dystrophy and Huntington’s chorea. There could be other chromosomal or genetic abnormalities which could be passed on to the children.
  • Who can be an egg donor?


  • Any healthy woman who is:

  • Less than 35 years old
  • Non-smoker
  • Not overweight (BMI less than 30)
  • No family history of genetic or inherited diseases
  • No history of mental illness


  • It is preferable for the donor to have had a healthy child (or children) of her own but not required. Egg Sharing Surrogacy Surgical Sperm Retrieval

    Holistic Treatments

    Nutritional Therapy

    We offers a wide array of IVF and assisted fertility treatment options, including:

  • Assisted Hatching
  • Complementary Therapies
  • Counseling Services
    • Donor Programs
    • Donating Sperm, Eggs, and Embryos
    • Using Donor Sperm, Eggs, and Embryos
  • Egg Freezing and Storage
  • Embryo Freezing and Storage
  • Endometrial Scratching
  • Frozen Embryo Transfer
  • Intra Uterine Insemination (IUI)
  • In Vitro Fertilisation (IVF) and Embryo Transfer
  • Intra-Cytoplasmic Sperm Injection (ICSI)
  • Male Infertility Treatment
  • Ovulation Induction
  • Pap Smears
  • Physiological Intra-Cytoplasmic Sperm Injection (PICSI)
  • Polycystic Ovarian Syndrome (PCOS) Treatment
  • Pre-Implantation Genetic Diagnosis (PGD)
  • Pre-Medical Treatment Semen Freezing
  • Pre-Vasectomy Semen Freezing
  • Pre-Pregnancy Information and Advice
  • Semen Analysis
  • Semen Freezing and Storage
  • Surgical Sperm Collection (SSC)
  • Transvaginal Ultrasound Scanning
  • Issues pertaining to egg donation

    Donors can be known or anonymous. A family member (sister or niece) or a close friend can act as an egg donor. The other option is to advertise and recruit anonymous donor. The long-standing debate is whether it is morally correct to pay the donors. In the UK, from 2012 legislation from the Human Fertilisation and Embryology Authority (HFEA), the UK regulator of fertility treatments, allows clinics to compensate donors (up to £750) for their travel and expenses. Another potentially controversial point is anonymity. Some donors would like to meet the recipient and to know what sort of person is going to receive her eggs. But this can lead to other social problems. Some donors do not wish to know or meet the recipient. They would like to know only the basic information about the recipient. Along the same lines, many recipients do not like to know or meet the donors. But, some would like to meet and know the donor before proceeding with the treatment. Who can be an egg donor?

    Any healthy woman who is:

  • Less than 35 years old
  • Non-smoker
  • Not overweight (BMI less than 30)
  • No family history of genetic or inherited diseases
  • No history of mental illness
  • It is preferable for the donor to have had a healthy child (or children) of her own but not required. Types of donor Altruistic egg donors

    Altruistic egg donors generously choose to donate their eggs for altruistic reasons. Altruistic egg donors are not paid but can be compensated for the expenses they incur in connection with the donation process, such as travel costs, accommodation, loss of earnings and childcare. Altruistic egg donors may receive compensation of up to £750 per cycle of donation. Should you choose to receive eggs from an altruistic donor in a fresh egg donation treatment cycle, we will allocate all of the eggs collected from that donor’s treatment cycle to you, i.e. you will not share the eggs with another recipient. Egg share donors

    Egg sharing is process whereby a woman who needs IVF shares half of the eggs collected during her treatment cycle with an anonymous recipient in return for heavily subsidised treatment costs. Frozen eggs from HSFC’s egg bank

    Due to recent advances in egg freezing techniques, which provide freezing and thawing success rates are over 90%, it is now not necessary to use fresh eggs for egg donation cycles. Harley Street Fertility Clinic has established an egg bank of frozen eggs from UK donors. One of the benefits of using frozen donor eggs from our egg bank is the lack of worry of the number eggs you might receive for your treatment: we guarantee a minimum of 10 mature frozen eggs for each treatment cycle. Frozen eggs do require fertilisation by intracytoplasmic sperm injection (ICSI) and the extra charge for this is included in our treatment cost for a recipient using frozen donor eggs. Screening of donors

    Egg donors initially have a consultation with a doctor who will take a detailed medical history and perform a physical examination. The doctor will explain the procedure involved in egg donation treatment. The donor will then see a nurse to fill out some basic information about herself. She will then be provided with a letter, containing a medical history form that she must complete and have confirmed by her GP. Once we receive the completed medical history form (provided everything is clear), the donor will be offered a session implications counselling, with an accredited fertility counsellor, to discuss the social and ethical issues pertaining to egg donation. The donor will also be asked to attend the clinic for a vaginal ultrasound scan and hormone blood tests between days 2 and 5 of her period. These tests are performed to assess the current fertility of the donor.

    All donors are then screened for the following:

  • Full blood count
  • Blood group and Rhesus type
  • HIV and HTLV
  • Hepatitis B and C
  • Syphilis (VDRL)
  • Cytomegalovirus virus (CMV) antibodies screening
  • Chromosomal analysis
  • Cystic fibrosis screening
  • High vaginal swab
  • Chlamydia and gonorrhoea (urine test)


  • In non-Caucasian donors, other screening tests are carried out in suitable cases:

  • Sickle cell tests for Africans
  • Thalassaemia screening for Asians and Mediterraneans
  • Taysach’s disease screening for Jews


  • Donors must inform the clinic of any medical information that may come to light after donation that may have health implications for any woman who receives treatment with their eggs or for any child born as a result of such treatment. The screening process may reveal previously unknown conditions or infections, some of which may be treatable. Donors’ chromosomes are screened and therefore previously unsuspected genetic disorders may be brought to light. We will arrange referral to Genetics Counselling and provide support. In some situations genetic disorders may affect other members of a donor’s direct family and we will discuss the relevant issues with the donor should these come to light. Immediately prior to starting her stimulation the donor will be screened once more for infectious diseases (HIV, Hepatitis B and Hepatitis C, Chlamydia, Gonorrhoea) by a new method called the nucleic acid amplification technique (NAT). In addition to providing a repeat set of results, this technique allows early detection of viral infections that may have a incubation period during which they cannot be detected by traditional methods (e.g. HIV can be dormant for up to 180 days).  

    Egg Sharing

    This is a form of egg donation which is mutually beneficial to both parties. When an infertile couple cannot afford the cost of IVF treatment, they share the eggs with another couple. The donor couple’s treatment is free. Criteria for being an egg share donor

  • Age between 21 and 35
  • Normal hormone profile (FSH less than 8 and E2 less than 200)
  • Body mass index (BMI) under 30
  • Non-smoker
  • No family history of inheritable disorders
  • Screen negative for infectious diseases, cystic fibrosis and normal karyotyping (single blood test)


  • Both the donor couple and recipient couple are advised to have independent counselling before commencing treatment.

    After the eggs are collected, they are shared between the donor couple and the recipient couple in a random fashion. The minimum number of eggs for sharing will be ten. If during the monitoring of ovarian stimulation, it becomes apparent that the donor is not producing enough follicles, the available options will be discussed with the donor couple. They can keep all the eggs for their treatment and pay for it. Alternatively, they can donate all the eggs to the recipient and have a free IVF cycle subsequently.

    Surrogacy Introduction Surrogacy refers to an arrangement when one woman carries a baby or babies for another woman/couple and hands over the baby after birth. This is called renting the womb. The couple who want the baby and start this arrangement are called the commissioning couple. The woman who carries the baby is called the surrogate or host.

    Who will benefit from surrogacy treatment?

  • Women born without a uterus
  • Women who have undergone a hysterectomy or removal of the uterus
  • Women with damaged uterine lining, including Asherman’s syndrome where the uterine cavity is obliterated due to adhesions as a result of severe scraping of the womb.
  • Women with recurrent miscarriages
  • Repeated failure of IVF treatment in spite of good quality embryos
  • Severe medical conditions incompatible with pregnancy


  • Surgical Sperm Retrieval (PESA and TESA)

    Introduction

    Surgical sperm retrieval is a technique for collecting sperm from the epididymis or testis. Procedure

    Percutaneous Epdidymal Sperm Aspiration (PESA) This is a simple procedure whereby sperm is aspirated from epididymis with a small needle. There is no cut involved in this procedure. After collecting the sample, it is examined under the microscope to confirm the presence of sperm. If this is not successful in retrieving sperm TESA is performed.

    Testicular Sperm Aspiration (TESA) Here the sperm is directly obtained from the testis with a small needle and suction applied with a small syringe. After the operation, there may be some discomfort and bruising for a few days. Pain killers such as Paracetamol or codeine tablets can be used to abate the discomfort. A firm scrotal support (tight underwear) is recommended for a few days after the procedure. This will prevent any bleeding and swelling of the scrotum.

    Who will benefit from PESA/TESA? Men with no sperm in the ejaculate (azoospermia) will benefit from this treatment. The two types of azoospermia are described below.

    Obstructive

    The sperm production in the testis is normal but there is a blockage in the tube (vas deferens) which carries the sperm from the testis. The blockage can be due to infection, congenital absence of vas deferens, previous vasectomy or failed vasectomy reversal. In such cases, there is a 70 to 80% chance of success.

    Non-obstructive

    Here there is no obstruction in the passage. Sperm production might take place in some pockets of testicular tissue only. In such cases, the chance of success is between 20 and 40%.