The following pages contains information regarding the third phase of receiving eggs..
- Hormonal Support after the Embryo Transfer
- The Pregnancy Test
- Risks (ER)
- Risks of ICSI
- Causes of failure (ER)
Hormonal Support after the Embryo Transfer
On the day of embryo transfer, you will be given a letter which will explain further essential hormonal support in the second half of your cycle. Firstly this helps your uterus prepare for the embryos better. Secondly we know that without any support, some women will bleed too early after an embryo transfer and before the embryo implantation has declared itself in the form of hormonal signals. Hence medication is given after the egg collection or embryo transfer to ensure that premature bleeding does not occur and that you have the best chance of maintaining an embryo implantation.
This support can be given in several ways and clinicians as well as patients can have their preferences:
Progesterone pessaries (Uterogestan or Cyclogest):
These are given in the dose of 200 mgms, 6 hrly or four times every 24 hours. They can also be used rectally as a suppository.
Advantages: Apart from the inconvenience of frequent vaginal and rectal administration, it is painless and easy to administer.
- The medication can flow out of the vagina or the rectum and hence not have the full benefit.
- The absorption of the hormone from the vaginal skin into your body can also vary between patients.
- Some patients may thus experience premature bleeding despite this support.
- Occasionally women can develop an allergic reaction to progesterone in the form of urticaria or skin rashes and sometimes the allergy can be severe.
Progesterone Injections (Gestone or Prontogest):
This is a daily intramuscular injection of progesterone.
- For some once daily administration is an advantage.
- It also ensures that premature bleeding does not occur. In fact most women would not have had bleeding until we do the pregnancy test 14-16 days after the embryo transfer.
- We have an unpublished observation that it provides some protection against the risk of OHSS. This has not been scientifically tested and hence we are conducting a prospective trial.
- This is a painful injection and causes local discomfort. We advise you to rotate sites of injection in order to ensure that no one site becomes excessively inflamed.
- Occasionally women can develop an allergic reaction to progesterone in the form of urticaria or skin rashes and sometimes the allergy can be severe.
- When you become pregnant, we continue this support in early pregnancy until placenta is well established in the uterus (normally at 9-10 weeks gestation).
Human Chorionic Gonadotrophin (Pregnyl, Gonasi, Ovitrelle):
This is a very potent hormone injection. One Injection is given on the day of embryo transfer and another is given three days later.
- It ensures that premature bleeding does not occur and there is no need for continued support in early pregnancy.
- There are only two injections and no other medication is needed during the 2nd half neither of the cycle nor in early pregnancy.
- There are no incidences of allergies.
- When given to all patients, this has been associated with an increased risk of ovarian hyperstimulation OHSS). NICE recommends that it should not be used.
The Pregnancy Test
When to come?
You are asked to come to TLCRM, 14 to 16 days after the embryo transfer for a pregnancy test, irrespective of whether you have menstruated or not. This involves you bringing an early morning urine sample. If this test is positive then we will ask you to return to us 2 or 3 weeks later for an ultrasound scan.
We obviously hope that every patient will become pregnant but in reality 55-70% patients depending on your age group do not conceive. You will understandably feel a sense of grief in the event of failure. Please do not hesitate to ask for help in the form of counselling support with our psychologists. We will also arrange a review consultation after the completion of each treatment cycle. At this time we will have an opportunity to discuss those factors that may have become apparent during your treatment and consequently may require modification in further attempts.
Risks with an egg donation cycle
There are no treatments that are completely free of risk. In an Egg donation cycle there are the following risks:
The risk of miscarriage after a positive pregnancy test alone is approximately 10-20%. This is no different to that after a normal conception. Once the pregnancy sac has been seen and the fetal heart action identified then the risk of miscarriage is substantially less. The risk of a congenital or genetic abnormality in babies born after IVF has not been higher than that in spontaneously conceived pregnancies. Your personal risk is more likely to relate to your age, your family history and whether or not you have a multiple pregnancy. Please see the section on multiple pregnancies inside on page … insert page no for further detail.
Risk of an ectopic pregnancy:
The embryos are not ready to implant at the time of their replacement. At that time they are in a very small volume of fluid which we expect to spread like a thin film on the surface of the lining of your womb. The embryo may sit in a fold of the lining of the uterus until it reaches the stage of implantation. The risk of embryo floating away in the direction of the fallopian tube exists in all patients. In normal circumstances we expect that the fine hair in the tube that beat in the direction of the womb will prevent such a migration. However in some cases this may not happen and the embryo enters the tube. Unable to return to implant in the uterus and especially in women with damaged tubes, it may attach itself to the tube and thus a tubal pregnancy occurs. If left undiagnosed, the tube may rupture and internal bleeding may take place. We endeavour to make an early diagnosis by performing an ultrasound scan at 7 weeks of pregnancy (3 weeks after your pregnancy test).
- It is therefore important to attend for the pregnancy test even if you have bled and for the scan after a positive test. If a pregnancy sac is not seen on scan, a blood test is taken to measure the pregnancy hormone (hCG) level in your blood. You may be asked to attend for more tests after a few days interval. If this level is rising or static then we may perform a laparoscopy.
- If you are unlucky and have a tubal pregnancy then you will require the removal of the tube. We may also counsel you regarding the future of your remaining tube in case it is already known to be irreparably damaged or is found to be such at surgery. We advise you to consider removal of both tubes in those circumstances in order to avoid a recurrence of this complication in future. This is an important decision as it is sterilising and no steps are taken with out your written consent and complete agreement.
- For the operation you will be admitted to St James’s to prevent an untoward occurrence whilst travelling. The risk of an ectopic pregnancy is approximately 3-4%.
- Occasionally you can have a combined intrauterine and an ectopic pregnancy (heterotopic pregnancy). These are more difficult to diagnose. If present then often but not always, the tubal pregnancy can be removed with out harming the uterine pregnancy.
- We perform a risk assessment for this complication too in our pre-assessments. If you are already known to have damaged tubes you may choose to have removal of the tubes (salpingectomy operation) performed before the treatment cycle in order to minimise the risk of this complication. This is a sterilising procedure and future pregnancies will only be possible after IVF. Therefore you have to be completely at terms with your infertility if you undertake this procedure. It is performed in most cases laparoscopically (key hole method) and you do not need prolonged recovery or delay to treatment
Risk of an unwanted normal or ectopic pregnancy:
We may not collect all eggs and therefore there is always some risk of an embryo forming naturally and leading to a pregnancy. You are advised to abstain in this cycle or use barrier forms of contraception at all times until you menstruate.
Risk of equipment failure:
The trust maintains service contracts for all equipment that is regularly serviced. There are also many standard operating procedures in the laboratory that help us have an early warning for problems. Despite all our efforts and very uncommonly equipment failure may sometimes lead to loss of eggs or embryos. This is a ‘Category A’ incident that will be immediately notified to HFEA, the trust and you. There would usually be a thorough investigation and steps taken to prevent a recurrence of similar problems. The HFEA also operates an Alert system which we use to learn from incidents elsewhere.
- Although some have raised alarm over the risk of ovarian cancer with the use of hormones, these preparations have been used in treatment since early 1960’s without any notified cases that can be directly liked to the use of these hormones. The available evidence suggests that there is no increase in your risk over and above that exists naturally. Infertility per se, delay in first pregnancy, and failure to breast feed, family history, obesity and smoking are known risk factors for the cancer of the ovary and the breast.
- There have been no cases of complications with protein impurities in the urinary preparations. Theoretically some have worried those external proteins when injected could transfer viruses or prions that could lead to an illness like CJD at a later date.
This section is there for your information and to reassure you that as far as we know none of the publicised risks have been scientifically confirmed.
Risks of ICSI
ICSI was pioneered by a group in Brussels in 1992 and hence since rapidly become accepted in IVF centres around the world. The oldest child is therefore still very young. It is a significant invasion into natural processes where a natural fertilisation and pregnancy would not have occurred, its long term risks are not known. It is therefore appropriate that you consider it an experimental procedure.
The risks described in this section reflect the current state of our knowledge and the guidance provided by the Human Fertilisation and Embryology Authority. We regularly update this section, as and when new information becomes available. Please read carefully and ask for clarification as and whenever necessary. We will be pleased to discuss this and any other issue with you in detail. Also note that this section deals with everything that we know to date and the contents of these sections will be subject to change and variation, as more information becomes available.
ICSI is an invasive technique and may also use sperm that would not otherwise be able to fertilise an egg. For these reasons, concerns about the potential risks to children born as a result of ICSI have been raised, and several follow-up studies have been published. These follow-up studies involve relatively small numbers of children and do not include effects that may be seen in older children or in the next generation. The HFEA considers follow-up studies to be extremely important and would encourage patients to talk to their treatment centre about participation in such studies. Clearly, more studies are needed, but the use of ICSI has been potentially linked with certain genetic and developmental defects as explained below:
A – Possible inheritance of genetic chromosomal abnormalities:
INCREASED INCIDENCE OF CYSTIC FIBROSIS (CF) MUTATION STATUS IN AZOOSPERMIC MEN
Some men who have no sperm in their semen (approximately 5-10% of men with azoospermia) are found to have Congenital Absence of Vas Deferens (CBAVD). In this condition, the tubes that carrry sperm from the testis to the penis are missing. Two thirds of men with CBAVD are also carriers of certain cystic fibrosis mutations. Men with CBAVD and their partners may therefore wish to undergo genetic testing before proceeding with ICSI. This is not compulsory as long as you are aware of and understand the risks of not taking this genetic test. It has also been recommended that genetic testing should be offered to other azoospermic men. Such a screening test may have to be performed locally via your GP.
Genetic counselling is strongly recommended for all azoospermic men with CBAVD along with their partners. This will help both for an improved understanding of your condition and also to become aware of implications of genetic testing.
MALE FERTILITY RELATING TO Y CHROMOSOME (SEX CHROMOSOME) DEFECTS
A small proportion of sub-fertile men have parts of the Y chromosome missing (deleted). Certain genes on the Y chromosome have been shown to be involved in the production of sperm, and deletions of these genes may be responsible for some men having few or no sperm in their semen. Consequently, using sperm with such deletions to create an embryo may result in the same type of sub-fertility being passed from father to his son. It is recommended that sub-fertile males and their partners contemplating ICSI treatment should be aware of this possibility.
SEX CHROMOSOMAL ANOMALIES
Abnormal numbers of structures of chromosomes, particularly the sex chromosomes (X and Y), may be associated with infertility in both men and women, and babies born from ICSI treatment may have a slightly increased risk of inheriting these abnormalities. Studies have found that up to 3.3% of fathers of ICSI babies have abnormal chromosomes. It is estimated that up to 2.4 % of the wider population have a chromosomal abnormality. Therefore, where ICSI is used in the treatment of men with severe azoospermia or oligospermia there is an increased risk of sex chromosome disorders. Sex chromosome abnormalities such as 47XXX: 47 XXY and 47XYY occur at a relatively high frequency in the neonatal populations – about 1 in 700 birth for each of the aforementioned abnormalities.
NOVEL CHROMOSOMAL ABNORMALITIES
The complexity of the process of egg and sperm production means that even if an individual possesses a normal number of chromosomes, their gametes could potentially have an abnormal number. It is not possible to detect beforehand which eggs or sperm have chromosomal abnormalities, and gametes that might not have been able to participate in natural fertilisation could therefore be used in ICSI. Babies born after ICSI have been reported to have new chromosomal abnormalities in 3% of cases. The rate in general population is around 0.6%.
B – Possible developmental and Birth defects
There is not as yet any clear evidence whether ICSI results in higher rates of birth defects. The number of babies reported to have major birth defects, such as cleft palate, is between 1-5% in both the general population and in babies born following ICSI. Studies suggest that minor abnormalities occur in up to 20% of ICSI babies, compared to up to 15% of the general population. More studies are needed in order to gain further insight into these possible effects.
One recent study that followed up a relatively small number of children has given an indication of possible delays in mental development at one year in some children born following ICSI. Other studies have not shown this link and further research is needed in this area.
c – Possible risks during pregnancy:
With ICSI, it is possible that abnormal gametes, which would not usually be able to produce a viable embryo could be used, increasing the chance of an abnormal embryo being formed. Many abnormal embryos will not implant into the womb and do not grow, but some might, leading to a possible higher risk of miscarriage. It has been reported that the risk of miscarriage increases in proportion to the severity of male infertility.
Common causes of failure
These are as follows:
- Failure to recruit optimum number of follicles with or without poor hormone levels.
- Premature release of the eggs (very uncommon)
- Unexpected illness
- Failure to Fertilise: This may be due to defective sperm, low number of sperm, functional abnormalities of the sperm, unknown technical failure and infection in the seminal sample (uncommon).
- Failure of Cleavage: Occasionally fertilised eggs fail to divide and continue their development. Not all fertilised eggs will cleave to form embryos.
Although these are common causes of failure, sometimes failure also occurs even when everything has apparently gone well. Sometimes we may not have an explanation for why a pregnancy fails to occur. Mostly in these cases the embryos have failed to maintain their growth and development because of indigenous, not necessarily repetitive genetic abnormalities. We know that the risk of genetic abnormalities in naturally formed embryos and In normal couples is nearly 50%. Embryos created in IVF cycles have the same incidence overall but this risk exponentially increases with age and is substantially increased in women at or above the age of 40 years.
Most genetically abnormal embryos fail to implant, maintain growth to become pregnancies or may miscarry after a positive test. In this situation usually the prognosis for future attempts is good and we will discuss any specific predisposing factors that you may have. We may consider the removal of hydrosalpinges (swollen tubes), endometrial polyps or fibroids (if present) in some cases before repeating the treatment cycle.