First trimester screening forthe fertility patient

RAD Magazine, 37, 432, 33-34

By Janet BrownFetal Medicine Specialist Sonographer

Advanced Clinical Specialist Sonographer,Queen Mary’s Hospital Roehampton,Lead Sonographer, Clapham SPMS

Infertility is defined as the failure to conceiveafter two years of regular, unprotected inter-course. It is estimated that 1 in 7 couples in theUK will experience some difficulty in trying toconceive. In the 20-45 year age group, problemswith fertility are the most common reason, asidefrom pregnancy itself, that most women visittheir GPs.

With major advances in fertility techniques, availability oftreatment – including more access on the NHS – and recentchanges in the law, more and more of the population is con-ceiving by assisted conception techniques.

Latest figures show (2007) 36,648 women patients under-went fertility treatment (IVF), which equates to 41,933cycles (HFEA 2007) (figure 1).

With IVF, the pregnancy rate is approximately 40%, witha live birth rate of approximately 23%. These are overallfigures, although detailed statistics may be quite differentfor different age groups and treatments.

In 2007, 11,268 babies were born as a result of IVF/ICSI.Approximately 1.8% of all babies born in the UK are as aresult of IVF/ICSI (HFEA 2007).

Carrying out routine first trimester screening, with cur-rent figures, one will undoubtedly encounter patients whohave undergone some form of assisted conception techniques.

As first trimester screening becomes more sophisticatedand sensitive, the requirement to input multiple data accu-rately often rests with the sonographer and it is crucial thatthose doing so have a very clear understanding of the para-meters required to maximise the sensitivity and efficacy ofthe screening programme.

The data required for those patients who have under-gone fertility treatment varies considerably from those con-ceiving naturally and as a result can markedly affectscreening results.

There are currently many different options of fertilitytreatment available. Some simply enhance monthly egg pro-duction, eg the administration of clomid or Tamoxifin (FSH),

or trigger ovulation, eg the administration of HCG. Thesepatients go on to conceive naturally (in vivo) after ovulationby intercourse, insemination with a prepared semen sam-ple with or without the use of ovarian stimulation. Thesetypes of treatment generally present as:

TI – Timed intercourse.AI(D) – Artificial insemination (with donor).IUI – Intrauterine insemination.For those who have undergone ovulation induction or

insemination techniques and fertilisation has occurred bythe natural process, even if they have taken gonadotrophins/drugs to manipulate their cycles and ovulation dates (oftenmaking LMP an inaccurate estimate of gestational age), thepregnancy should always be dated by CRL between 11-14weeks in accordance with current NICE guidelines.

The risk assessment should have a requirement for ovu-lation induction which should also be completed. The admin-istration of HCG will have an effect on the MoM value ofthe PAPP-A and Bhcg.

Ovulation will be induced only by the administration ofHCG immediately prior to ovulation. Taking gonadotrophinsto stimulate the ovaries does not trigger ovulation.

The following are the main types of interventional fertil-ity treatments with which patients may present and allshould be taken in to account when inputting data for firsttrimester screening.

In vitro fertilisation (IVF) requires the harvesting ofeggs, generally from ovaries that have undergone super-ovulation, mixed with prepared sperm and left for 24 hoursin an incubator to allow fertilisation to occur.

Intracytoplasmic sperm injection (ICSI) again usesmature harvested eggs and the injection of a single spermmicroscopically. This is used generally in couples where thefertility issue lies with the male or where there have beenpreviously poor rates of fertilisation.

Frozen embryo transfer (FER or FET) involves a pre-viously created and frozen embryo, defrosting and implant-ing directly into the uterine cavity (most commonly underultrasound guidance).

Pre-implantation diagnosis (PGD) allows for a singlecell to be removed from a developing embryo, created invitro and the chromosomes examined for normality. This isused generally for inherited conditions and currently notwidely available in the UK. In 2007 there were 39 live

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FIGURE 1Trends in IVF.

FIGURE 2Drop-down screen for conception options (Astraiaversion 1.20).

births as a result of PGD.Assisted hatching (AH) involves creating a small hole

in the zona pellucida (the outer layer) of the embryo usinga weak acid, micro laser or micro tool. This procedure hasnot been seen to improve pregnancy rates but is sometimesused after previously failed IVF cycles, particularly in olderwomen using their own eggs, where the zona is generallyseen to be harder.

The two MOST important factors are the dates of con-ception and the age of the egg provider at the time of eggproduction.

For IVF/ICSI pregnancies, these pregnancies should NOTbe dated by CRL. The date of conception should be used tocalculate the gestational age. The standardisation for thisis to use the date of egg collection as the day of conception.

The type of fertility technique should also be included atthis point (techniques may have a bearing on the risk).Embryo transfer dates should not be used as the date ofconception.

Embryos may be transferred at 2 or 3 cell stage or fivedays post-fertilisation as a blastocyst so, again, the date theeggs were harvested to create the embryos is used as a dateof conception to calculate the gestational age.

If frozen embryos have been transferred, things become alittle more complicated!

The cell stage the embryos were frozen at needs to beascertained and the day of conception calculated by workingback to an egg collection date. Compounding this is the pos-sibility that, once defrosted, the embryos may have beenallowed to continue dividing before transfer, so be sure toestablish at what stage the embryos were transferred.

A patient may arrive for screening with documented evi-dence of a pre-calculated EDD from their fertility clinic.

In 2006, 1,329 babies were born as a result of donorgametes received in the UK. Approximately 500 of thesewere from donor eggs. Donors providing gametes are care-fully screened.

However, there is an approximately 1% higher than nat-ural conception fetal abnormality rate with IVF/ ICSI. Inthe UK, currently you may only donate eggs by egg sharingwhereby you can share your eggs with a recipient for agreatly reduced cost to yourself for fertility treatment, oryou may donate altruistically. This means the supply ofdonor eggs in the UK is limited.

Very many patients using donor eggs will have travelledoutside the UK for their treatment. Some of them may havebeen absent at the time of fertilisation so it is important toestablish the correct dates; often the date when the partnerwas required to produce his sample is well remembered;this will almost certainly be the day of egg collection.

Once donor eggs are selected, a further option to inputthe donor’s date of birth is required; clearly this is a crucialpiece of data. Patients generally know the age of their

donors even if they are unsure of the exact date of birth, sodefault to the first of the first and use the donor’s year ofbirth.

When frozen embryos are used, whether donor or thepatient’s own eggs, the date the eggs were collected needs tobe input to give the age of the egg producer at the time ofembryo creation.

Most women having IVF/ICSI over the age of 43 yearswill be using donor eggs, as success rates with their owneggs tends to be very poor – about 4%. However, there arealso considerable numbers in the younger age groups whomay have also used donor eggs, eg those with TurnerSyndrome or premature ovarian failure.

Egg donation still remains a very controversial and sen-sitive issue for many patients. They themselves may beunaware of the significance of having used donor eggs totheir first trimester screening test.

Once it is confirmed that a patient has had IVF, itbecomes good practice to ask patients if they have used theirown or donor eggs and that sonographers allow them toanswer this question completely confidentially.

Many recipients of donor gametes do not wish even closefamily members to know. It is also important to point outthat use of donor eggs will be evident on any screeningreports you issue.

The single greatest risk associated with fertility treat-ment is multiple births. Currently a maximum of twoembryos can be transferred for women under 40 years andthree embryos for women over 40 years using their owneggs. The HFEA (Human Fertilisation and EmbryologicalAuthority) has launched a new national strategy to reducethe number of multiple pregnancies as a result of IVF from24% to 10% over three years. This is largely aimed at replac-ing one embryo per cycle. 32% of two-embryo transfers willresult in a twin pregnancy.

It is not possible to diagnose zygocity from ultrasound(unless a patient has had only one embryo replaced andthere is a resulting twin pregnancy or, later in a pregnancy,the two fetuses are seen to be of discordant sex).

It is estimated that there is at least a twofold rise in theincidence of monozygotic twining (0.9% against a naturaloccurrence of 0.4%) after assisted conception compared withnatural conception and this is higher with ICSI and blasto-cyst transfer than with standard IVF. Currently, the rea-son for this is unclear (S Vitthala et al, 2009).

32% of two-embryo transfers will result in a twin preg-nancy. The reasons for this remain unclear, although clearlythe fact that natural conception has not occurred is believedto have an effect.

Most patients will have a viability scan at their fertilityclinic between 6-8 weeks; however, of that group with aviable pregnancy, 30% of these pregnancies will fail in thefirst trimester.

It is quite normal to observe ovaries quite enlarged andeven with a small amount of free pelvic fluid up until 12-14

FIGURE 3Drop-down screen for donated gamete options(Astraia version 1.20).

FIGURE 4Enlarged ovary with multiple resolving luteal cystsat 12 weeks gestation.

weeks after ovarian stimulation. This is a normal appear-ance seen in the first trimester of multiple resolving lutealcysts after super ovulation. It is not hyper stimulation.

Finally, remember when giving risk values to patientswho have achieved their pregnancy through fertility treat-ment that, as with all patients, it is an individual and per-sonal risk for that pregnancy. Possibly, having come on avery long journey to reach first trimester screening, theirperception of high and low risk may differ markedly fromthat of the general pregnant population. It is the role of thescreening sonographer to allow them to make an informedchoice having received a clear explanation of the facts.

ReferencesNICE guidelines (2008) antenatal guidelines and NSC 2009.Astraia software GmbH, Occamstr. 20. 80802. Munich, Germany.Human Fertilisation and Embryological Authority.

http://www.hfea.gov.uk/fertility-treatment-trends.htmlS Vitthala, T A Gelbaya, D R Brison, C T Fitzgerald, L G Nardo. The risk

of monozygotic twins after assisted reproductive technology; a systematic reviewand meta-analysis. Human reproduction Update 2009 45-55.