Aston University, Birmingham (Aston)
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Cell signalling and physiology
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Contraception and infertility
Contraception.
Contraception = prevention of pregnancy before foetal implantation.
Sometimes this may be after fertilisation has occurred.
Aim of contraception is to prevent pregnancy.
Only way to make sure pregnancy 100% will not happen is by abstinence.
However, if abstinence is not maintained then to prevent pregnancy you can block
the access of sperm to the egg.
On the other hand, we can use knowledge of hormonal control of reproduction and
how we can disrupt the female reproductive cycle and prevent normal reproductive
events from taking place.
Female reproductive cycle.
There are several stages during this cycle that we can intervene with hormonally to
prevent pregnancy.
We can prevent follicle development. - if we prevent follicles from growing during
the follicular phase of the reproductive cycle, then we will prevent ovulation. If there
is no ovulation, then this means that pregnancy cannot occur.
Alternatively, after ovulation has happened and the corpus luteum forms from the
remaining follicle, if we block the corpus luteum from forming or if we promote its
degeneration, then we can also prevent pregnancy.
Another alternative is to prevent implantation, we can make the endometrial lining
of the uterus unreceptive, so even if the egg is released and fertilised then the
resulting blastocyst cannot implant.
All of these interventions can be achieved if we disrupt the normal functioning of the
HPG endocrine axis.
Female HPG axis.
We have a stimulus, and the signal will be received by the hypothalamus, and the
arcuate nucleus within the hypothalamus will secrete GnRH.
The GnRH will travel to the anterior pituitary and stimulate the gonadotrophs within
the anterior pituitary to secrete two gonadotrophic hormones: luteinising hormone
(LH) and follicle stimulating hormone (FSH).
These two hormones will then travel to the ovary, and they will stimulate the ovary
to secrete the hormone inhibin and oestrogens and progesterone.
We have feedback from the gonadal hormones, inhibin can feedback to the anterior
pituitary and prevent the release of LH and FSH.
And both oestradiol and progesterone can feedback both positively and negatively to
the upstream components of the axis depending on their levels and also when in the
cycle those signals are received.
Hormonal contraceptives
Combined oral contraceptives:
Contain synthetic forms of oestrogens and progesterone.
They function by maintaining sustained levels of these two hormones, throughput
the reproductive cycle.
, By maintaining sustained levels of both oestrogens and progesterone’s we can mimic
pregnancy.
Pregnancy inhibits the female reproductive cycle by inhibiting the function of the
HPG axis.
With combined oral contraceptives, treatment can be started on any day of the
cycle.
But if they are started after cycle day 5, then protection from pregnancy will not
start straight away. Therefore, other forms of contraception should be used.
Most common forms of oral contraceptives- they are taken for 21 days and then not
taken for 7 days.
During the 7 days most women will experience a period.
By taking exogenous forms of both oestrogen and progesterone, the levels of both of
these hormones are going to remain the same throughout the cycle. This is going to
affect the normal functioning of the HPG axis.
The oestrogen component of the combined oral contraceptive has an effect on
inhibiting the HPG axis both at the level of the hypothalamus to inhibit
gonadotrophin releasing hormone release, and also at the level of the anterior
pituitary to prevent the secretion of follicle stimulating hormone and luteinising
hormone.
This is going to have effects on cells within the ovary and the uterus.
Within the ovary the effects of steady levels of oestrogen throughout the cycle
inhibits follicle maturation and as a result of this will inhibit ovulation.
The oestrogen component is also going to inhibit the formation of the corpus luteum
in the ovaries.
The progesterone only component of the combined pill, inhibits gonadotrophic
hormone release from the anterior pituitary and will contribute with the oestrogens
to inhibit ovulation.
Primary mechanism of action of the progesterone component of the combined pill in
preventing pregnancy is that they thicken the mucus lining the cervix. This makes it
very difficult for sperm to penetrate through and reach any ovum that has been
released during ovulation.
Hormonal contraceptives can also modify fertility by affecting motility in the oviduct.
The oviducts have ciliated epithelium, and the beating of the cilia facilitate the travel
of the ovum down the oviducts to the uterus.
The combined oral contraceptive makes the cilia beat faster so the ovum travels to
the uterus more quickly.
The sustained levels of oestrogen and progesterone are also going to have an effect
on the endometrial lining. As a result of this the endometrium becomes thinner and
less responsive to implantation should fertilisation occur.
S
Efficacy of combined oral contraceptives: they have a very low failure rate. And if
they do fail as a contraceptive, it is usually caused by missed doses or drug
interactions, some antibiotics will interact with the oral contraceptive and make it
ineffective.
Patients who are taking the combined oral contraceptives may be at higher risk of
pregnancy if they experience gastrointestinal issues.
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