Grace Laporta U1839904
BS374 Modern approaches to human disease
Question 2 Summarise the critical steps involved in IVF treatment and explain how these may be
varied to accommodate the needs of particular people or couples. Include an evaluation of the
pros and cons of the procedures considered and comment on any major ethical issues that they
may raise.
Introduction
In vitro fertilisation was one of the major advancements of the 20 th century since the birth of the first
IVF baby Louise Brown in 1978 (1). IVF was first developed for female patients with tubal disease (2)
which is a disorder in which there is a blockage or damage to the fallopian tubes. This prevents the
oocyte from reaching the uterus from the ovary and becoming fertilised by a sperm. However, in
recent years IVF has been used to treat many forms of infertility including endometriosis and male
subfertility. IVF is still considered a relatively new field with great progress being made as records
show in 2018 68,724 IVF cycles were undertaken with a 26% chance of live birth per embryo
transferred (3) making IVF 54% more likely to be successful compared to 1991. However, the live
birth rate needs to be improved to accommodate for all types of infertility and give the chance of
being a parent to as many couples as possible.
Ovarian stimulation
Ovarian stimulation is the first step of IVF carried out to increase the number of eggs which are
released in ovulation so more eggs can be retrieved during egg retrieval. The treatment consists of
injecting follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH) 8-10 days after the end
of the previous period. However, when IVF is used to treat male infertility, ovarian stimulation is not
recommended as the rate of multiple pregnancies increases without a significant rise in the overall
pregnancy rate (4). Ovarian stimulation can also cause ovarian hyperstimulation syndrome (OHSS),
which causes the ovaries to swell and become painful which is more common with injected
hormones (5). In addition, ovarian stimulation is also linked to an increased risk of ovarian cancer,
particularly borderline ovarian tumours (6).
Egg retrieval
The next step is egg retrieval which is a surgical process aimed at extracting oocytes from the ovarian
follicles mainly performed under anaesthesia using transvaginal ultrasound aspiration. An ultrasound
probe is inserted into the vaginal cavity to identify follicles, and a needle is guided through the
vagina and into the follicles during this procedure. The eggs are extracted from the follicles using a
needle attached to a suction device. Clinical consent forms are filled out by the planned parents
before the development of the embryos, at a time when the patients' main concern is optimising the
chances of their future IVF cycle being successful. However careful consideration is required to
determine the use of their unused embryos. As there could be complications following divorce as
only one partner might want to use them. The egg retrieval technique is more complex, difficult, and
risky in obese patients so patients over 50 BMI are not permitted to have IVF treatment (7).
Figure 1 During oocyte extraction, a
haemorrhagic condition on the artery of the left
ovary occurred. Showing the risks occurred with
Egg retrieval (Zaami, S. et al., 2020)
, Grace Laporta U1839904
BS374 Modern approaches to human disease
Acute ovarian haemorrhage is also a risk (0.04–0.07%), caused by a vascular disruption in the uterus,
ovary, or iliac vein, but when they occur, they may need surgical intervention and are more common
in lean polycystic ovary syndrome patients (8). The anaesthesia also has an increased risk of
bradycardia and bradypnea so anaesthetics must be monitored carefully for patients who have heart
conditions (9).
Sperm retrieval
Sperm preparation (SP) involves separating functional sperm from non-motile and viable sperm and
the seminal plasma. Variations of sperm separation techniques are needed in clinical practice with
success based on ejaculate quality (10). The swim-up test (11) takes advantage of the sperms
tendency to swim against gravity. The seminal plasma is overlayed with 1ml of culture media at 37
°C for 40 mins (fig 2). Motile spermatozoa swim to the top of the tube so taking 1ml from the top
will provide the most motile sperm, not in the seminal plasma. Another method, density gradient
centrifugation is where seminal plasma is placed on two different concentration layers of (PVP)-
coated silica particles Percoll® and centrifuged for 15-30mins (fig 2). Highly motile spermatozoon
migrate towards the sedimentation gradient, thus penetrating the boundary faster than non-motile
cells. Resulting in a higher concentration of motile sperm in the bottom soft pellet, while the debris
and dead sperm collect at the interface and don’t pellet out. The density gradient method is
preferable for cases of extreme oligozoospermia or asthenozoospermia as it doesn’t require sperm
to be as motile as the swim-up test which is used for normozoospermic samples. When the seminal
fluid contains infectious agents, the density gradient centrifugation accompanied by the Swim-up
procedure can be used to remove the infectious agent (12).
Figure 2 A diagram to show the swim-up (horizontal progression) and density gradient method for sperm retrieval. The
swim-up test giving 2 layers of the spermatozoon with the motile sperm in the cultural media at the tops of the tube. The
density gradient results in motile sperm in the top gradient compared to the other gradients. Modified image from Male
exams - Genera Salute (generaroma.it)
BS374 Modern approaches to human disease
Question 2 Summarise the critical steps involved in IVF treatment and explain how these may be
varied to accommodate the needs of particular people or couples. Include an evaluation of the
pros and cons of the procedures considered and comment on any major ethical issues that they
may raise.
Introduction
In vitro fertilisation was one of the major advancements of the 20 th century since the birth of the first
IVF baby Louise Brown in 1978 (1). IVF was first developed for female patients with tubal disease (2)
which is a disorder in which there is a blockage or damage to the fallopian tubes. This prevents the
oocyte from reaching the uterus from the ovary and becoming fertilised by a sperm. However, in
recent years IVF has been used to treat many forms of infertility including endometriosis and male
subfertility. IVF is still considered a relatively new field with great progress being made as records
show in 2018 68,724 IVF cycles were undertaken with a 26% chance of live birth per embryo
transferred (3) making IVF 54% more likely to be successful compared to 1991. However, the live
birth rate needs to be improved to accommodate for all types of infertility and give the chance of
being a parent to as many couples as possible.
Ovarian stimulation
Ovarian stimulation is the first step of IVF carried out to increase the number of eggs which are
released in ovulation so more eggs can be retrieved during egg retrieval. The treatment consists of
injecting follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH) 8-10 days after the end
of the previous period. However, when IVF is used to treat male infertility, ovarian stimulation is not
recommended as the rate of multiple pregnancies increases without a significant rise in the overall
pregnancy rate (4). Ovarian stimulation can also cause ovarian hyperstimulation syndrome (OHSS),
which causes the ovaries to swell and become painful which is more common with injected
hormones (5). In addition, ovarian stimulation is also linked to an increased risk of ovarian cancer,
particularly borderline ovarian tumours (6).
Egg retrieval
The next step is egg retrieval which is a surgical process aimed at extracting oocytes from the ovarian
follicles mainly performed under anaesthesia using transvaginal ultrasound aspiration. An ultrasound
probe is inserted into the vaginal cavity to identify follicles, and a needle is guided through the
vagina and into the follicles during this procedure. The eggs are extracted from the follicles using a
needle attached to a suction device. Clinical consent forms are filled out by the planned parents
before the development of the embryos, at a time when the patients' main concern is optimising the
chances of their future IVF cycle being successful. However careful consideration is required to
determine the use of their unused embryos. As there could be complications following divorce as
only one partner might want to use them. The egg retrieval technique is more complex, difficult, and
risky in obese patients so patients over 50 BMI are not permitted to have IVF treatment (7).
Figure 1 During oocyte extraction, a
haemorrhagic condition on the artery of the left
ovary occurred. Showing the risks occurred with
Egg retrieval (Zaami, S. et al., 2020)
, Grace Laporta U1839904
BS374 Modern approaches to human disease
Acute ovarian haemorrhage is also a risk (0.04–0.07%), caused by a vascular disruption in the uterus,
ovary, or iliac vein, but when they occur, they may need surgical intervention and are more common
in lean polycystic ovary syndrome patients (8). The anaesthesia also has an increased risk of
bradycardia and bradypnea so anaesthetics must be monitored carefully for patients who have heart
conditions (9).
Sperm retrieval
Sperm preparation (SP) involves separating functional sperm from non-motile and viable sperm and
the seminal plasma. Variations of sperm separation techniques are needed in clinical practice with
success based on ejaculate quality (10). The swim-up test (11) takes advantage of the sperms
tendency to swim against gravity. The seminal plasma is overlayed with 1ml of culture media at 37
°C for 40 mins (fig 2). Motile spermatozoa swim to the top of the tube so taking 1ml from the top
will provide the most motile sperm, not in the seminal plasma. Another method, density gradient
centrifugation is where seminal plasma is placed on two different concentration layers of (PVP)-
coated silica particles Percoll® and centrifuged for 15-30mins (fig 2). Highly motile spermatozoon
migrate towards the sedimentation gradient, thus penetrating the boundary faster than non-motile
cells. Resulting in a higher concentration of motile sperm in the bottom soft pellet, while the debris
and dead sperm collect at the interface and don’t pellet out. The density gradient method is
preferable for cases of extreme oligozoospermia or asthenozoospermia as it doesn’t require sperm
to be as motile as the swim-up test which is used for normozoospermic samples. When the seminal
fluid contains infectious agents, the density gradient centrifugation accompanied by the Swim-up
procedure can be used to remove the infectious agent (12).
Figure 2 A diagram to show the swim-up (horizontal progression) and density gradient method for sperm retrieval. The
swim-up test giving 2 layers of the spermatozoon with the motile sperm in the cultural media at the tops of the tube. The
density gradient results in motile sperm in the top gradient compared to the other gradients. Modified image from Male
exams - Genera Salute (generaroma.it)
