Reproduction Flashcards
1
Q
When does ovulation occur?
A
Day 14 in a 28 day cycle
2
Q
What is the corpus luteum and what does it produce?
A
The structure left in the ovary after the egg has been released. It produces oestrogen and progesterone.
3
Q
Which hormone peaks 36 hours before ovulation?
A
Luteinising hormone
4
Q
Which functional group do oestrogens have that other steroid hormones do not?
A
An aromatic ring
5
Q
What are the common properties for all major classes of steroid hormone?
A
- 2 binding sites, one for DNA and the other for steroid
- binding of steroid ligand produces a complex that acts on DNA
- binding of DNA complex to DNA sites alters the combination of genes being expressed by target cells
- defines steroid receptors as transcription factors
6
Q
Why do gonadotrophins need receptors at the cell surface?
A
To eventually produce effects that are seen
7
Q
Describe the function of GnRH
A
- acts at GnRH receptor (it is a GPC receptor)
- release of hormones is pulsatile
- stimulates the release of FSH and LH
8
Q
What kind of frequencies is FSH stimulated by?
A
Slow GnRH pulse frequencies
9
Q
What of frequencies if LH stimulated by?
A
Fast GnRH pulse frequencies
10
Q
Give a use of GnRH agonists and antagonists
A
Used in ART to shut down the ovary in advance of a controlled cycle of ovulatory stimulation
11
Q
What is Buserelin and what is it used for?
A
Buserelin is an antagonist at GnRH receptor, it reduces production of FSH and LH.
Gives a contraceptive effect and is used in HRT
12
Q
What are the consequences of long term Buserelin use?
A
- GnRHR down regulation
- insensitivity to GnRH
- loss of production of FSH and LH
13
Q
Which hormone is released as levels of fat increase in girls?
A
Leptin
14
Q
What does Leptin do?
A
Stimulates kisspeptin neurone to stimulate GnRH neurons to produce GnRH
15
Q
What is early puberty associated with?
A
Higher risks for osteoporosis but lower risks for breast cancer
16
Q
Describe the early follicular phase
A
There is low oestrogen, the follicle hasn’t really grown.
No negative feedback to the hypothalamus.
There are slow GnRH pulses giving rise to high levels of FSH and lower levels of LH
17
Q
Describe the mid follicular phase
A
Oestrogen rises, there is negative feedback to the hypothalamus.
FSH is suppressed due to negative feedback.
Positive feedback as oestrogen increases at another areas in the hypothalamus
GnRH pulses increase
18
Q
Describe the late follicular phase
A
Oestrogen and progesterone feedback negatively
High oestrogen and progesterone suppress the production of gonadatrophins
Positive feedback by steroid to the hypothalamus is followed by negative feedback
19
Q
Describe steroid hormone action
A
Binding of steroid complex to the steroid response element (SRE) on DNA alters the rate of transcription so mRNA abundance is also altered
20
Q
What happens when oestrogen binds to its receptor?
A
The receptor undergoes a conformational change, this can affect binding to DNA or its ability to recruit co-factors.
21
Q
MoA of Faslodex
A
Binds to oestrogen receptor and blocks its ability to activate target genes. It binds in preference to estradiol
22
Q
MoA of Tamoxifen
A
partial agonist/antagonist used for breast cancer, it is effective on oestrogen in the breast but not in the endometrium
23
Q
Define menstruation
A
Shedding of superficial layer of endometrium
24
Q
What does withdrawal of sex steroid lead to?
A
Vasoconstriction
Tissue hypoxia
Connective tissue breakdown
Fragmentation
25
Define endometriosis
The establishment and growth of endometrial tissue outside the uterus
26
What causes endometriosis?
Reflex menstruation - endometrial tissue fragments shed at menses passing through the fallopian tube then becoming established in ectopic sites
27
What are the symptoms for endometriosis?
Pelvic pain and infertility
28
What are the treatment options for endometriosis?
Surgical removal
Pain medication
Pharmacological blocking of hormone cycle with an aromatase inhibitor, COC or GnRH modulators
29
Define interstitial implantation
Implantation of developed blastocyst (the implantation window is ~4 days)
30
What produces hCG?
The placenta produces hCG from the hatched blastocyst stage
31
Where is hCG measurable?
Maternal blood and urine - only after implantation
32
What happens if implantation is too late?
The corpus luteum regresses and pregnancy fails
33
What is the role of progesterone in pregnancy?
Regulates the transport of egg/embryo though the fallopian tubes.
Prepares the uterus to receive implanting blastocyst
Sustains uterine lining throughout pregnancy
Inhibits myometrial contractility
34
What happens at 7-9 weeks of pregnancy?
The placenta takes over production of oestrogen and progesterone from the CL - luteoplacental endocrine switch
35
What what point are miscarriages most likely?
At the luteoplacental endocrine switch, if abnormal placentas are produced they can't produce the hormones required
36
At what point is a pregnancy viable?
From when the heart pulsations can be visualised within gestation sac
37
When can a transvaginal ultrasound be done?
5 weeks after last menstrual period
38
When can a transabdominal ultrasound be done?
6 weeks after last menstrual period
39
Why does ectopic pregnancy occur?
Occurs due to tubal infection / upper reproductive tract infection. Humans have a short cervix and so it doesn't work as effectively as other animal species.
40
Which drug is used in ectopic pregnancy?
Methotrexate - used to prevent cell proliferation (blocks DNA synthesis)
41
What is mifepristone used for?
Termination of pregnancy
| Structurally similar to progesterone and binds to its receptor but exerts different effects
42
How does mifepristone work?
Blocks preparation of endometrium for pregnancy
| Counteracts effect of progesterone on myocetrial contractility
43
What does human placental lactogen (hPL) do?
Modulates intermediary metabolism by changing the level of insulin-like growth factor (IGF). Increases glucose and amino acid availability to foetus
44
What occurs in the embryonic stage?
Formation of major organs - lasts up to 10 weeks
45
What occurs in the foetal stage?
Maturation, development and growth - lasts 10 - 38 weeks
46
How is progesterone involved in labour?
Progesterone suppresses myometrial contractility till late pregnancy - the receptor is switched and the inhibitory receptor is lost.
47
How does the foetus stimulate labour?
Surfactants in the lung
48
What it oxytocin and how does it work?
Oxytocin is a peptide hormone released from the posterior pituitary gland.
Levels rise in the last trimester
49
How is oxytocin used?
Used with prostaglandin analogues to induce labour
50
What is used to mature foetal lungs in labour induction?
Glucocortioid treatment
51
Can drugs be used in pregnancy?
With caution but avoid anyway
Most drugs diffuse across the placenta and enter foetal circulation e.g. lipophilic, weakly basic drugs and larger molecules
52
What are tocolytics used for?
Prolonging pregnancy for up to 48 hours
53
What is a monophasic oral contraceptive?
Each pill has the same level of hormone
54
Give examples of monophasic 21 day pills
Microgynon 30, Yasmine, Cilest
55
What is Microgynon made up of?
Ethinylestradiol and Levonorgestrel
56
Give an example of a monophasic 28 days pill
Microgynon 30 ED
57
What is a phasic oral contraceptive?
Phasic pills contain two or three sections of different coloured pills in a pack. Each section contains a different amount of hormones.
58
Give an example of a 21 day phasic pill and what is its composition?
Logynon
| Ethinylestradiol and Levonorgestrel
59
Give examples of 28 day phasic pills and their composition
Logynon ED - Ethinylestradiol and Levonorgestrel
| Qlaira - Ethinylestradiol and Dienogest
60
What are the 2 types of POP?
3 hour - traditional progesterone, has to be taken everyday within the same 3 hour window
12 hour - desogesterel, must be taken within 12 hours of the same time each day
61
What is the difference between COC and POP in terms of number of pills and taking them?
POP need to be taken every day, there is no pill free period
62
Give an example of a traditional POP
Noriday - noresthisterone
63
Give an example of a newer POP
Cerazette - Desogestrel
64
Give examples of non oral COCs
Contraceptive patches (Evra)
- 1 patch every 7 days for 21 days
Vaginal ring (NuvaRing)
- 1 ring for 3 weeks
65
Give examples of POCs
Injection (Depo Provera - every 13 weeks)
Contraceptive implant (Naxplanon - every 3 years for 18-40 y/os)
IUS (Mirena every 5 years OR Jaydess every 3 years
66
What is the mechanism of action for CHCs?
Primary action is to inhibit ovulation, they thicken cervical mucus and alter the endometrium.
Oestrogen causes endometrial proliferation and Progestogen opposes proliferation
67
What is the mechanism of action for POCs?
They suppress ovulation by thickening the cervical mucus, they delay the transport of the ovum - affect the way cilia work.
They change the environment of the endometrium to make implantation unlikely.
68
Which contraceptive methods have a high risk of user failure?
Pill
Patch
Vaginal ring
69
Which contraceptive methods are independent of user (LARCs)?
Injection
Implant
IUD and IUS
70
Give examples of non hormonal contraceptive methods
Male / female condom
Diaphragm/cap + spermicide
Natural family planning
Sterilisation
71
Define lactational amennorhoea
Temporary postnatal infertility that occurs when a woman is amenorrheic and fully breastfeeding.
Up to 98% effective
72
What are the advantages of CHCs?
- menstrual period regular, lighter and less painful
- decrease in acne, functional ovarian cysts and benign ovarian tumours
- decreases risk of ovarian, uterine and colon cancer
73
What are the disadvantages of CHCs?
- Minor ADRs
| - increases risk of high BP, MI, stroke, VTE, breast cancer and cervical cancer
74
What are the advantages of POCs?
- High efficacy
- suitable when COCs aren't
- decreased risk of endometrial cancer
75
What are the disadvantages of POCs?
- ADRs
| - menstrual irregularities
76
What is classed as a missed COC pill?
> 24 hours
77
What is classed as a missed POC pill?
3 hours late for tradition
| 12 hours late for newer
78
When is EHC indicated for missed COCs?
If 2 or more are missed in >24 hours and UPSI occurs
79
What is advice for missed POP?
Continue pills with 2 days of barrier protection
80
When is EHC indicated for missed POCs?
If 1 or more active pills are missed and UPSI occurs before 2 tablets have been taken correctly
81
What is the UKMEC Category 4?
UK medical eligibility criteria
| Category 4 - a condition which presents an unacceptable health risk if a contraceptive is used.
82
What are the UKMEC Category 4 conditions?
```
Breast feeding women
Women >35 y/o + 15 cigarettes a day
Multiple CVS risks
Consistently elevated BP
Vascular disease and history of VTE
Migraine with aura
Current breast cancer
DM w/ nephropathy, retinopathy or neuropathy
Benign hepatocellular adenoma and malignant hepatoma
```
83
What is the advice for starting on COC?
Start on day 1 of natural cycle
If starting on day 1-5, no additional precautions needed
Quick starting (> day 6) then use additional precautions for 7 days
84
What is the advice for starting traditional POPs?
Start at anytime, no extra precautions needed
85
What is the advice for starting newer POPs?
If starting on day 1-5 no precaution needed
| But if starting > day 6, additional precaution needed for 2 days
86
Changing from COC to POP?
Make sure previous contraception has been taken effectively OR exclude pregnancy. Additional precaution needed for 2 days if in pill free period.
87
Changing from COC non ED to POP?
For immediate cover, ignore PF period and start immediately
88
Changing from COC to Cerazette?
For immediate cover, no need for PF period
89
Changing from POP to Qlaira?
Additional precautions for 9 days
90
Changing from POP to Zoely and other COC?
Additional precautions for 7 days
91
What are the types of emergency contraception?
IUS - up to 120 hours post UPSI
ellaOne - up to 120 hours post UPSI
Levonelle - up to 72 hours post UPSI
92
Which forms of contraception do DDIs with enzyme inducers occur?
Patches
Vaginal rings
Oral tablet
Implant
93
Which forms of contraction have no DDIs with enzyme inducers?
Injection
IUS
IUD
94
Which drugs decrease the effectiveness of contraceptives through DDIs with hepatic enzyme induction?
```
Carbamazepine
Oxcarbazepine
Phenytoin
Phenobarbital
Primidone
Topiramate
Neviprine
Ritonivir
Rifabutin
Rifampicin
```
95
Which CHCs are first line?
Microgynon 30 Ed
Brevinor
Marvelon
96
Which CHCs are second line?
Cilest
Logynon
Loestrin
97
Which CHCs are third line?
Evra - patch
| Better for younger patients
98
Which POCs are first line?
Micronor
| Depo-Provera (injection, but not for adolescents)
99
Which POCs are second line?
Cerazette
| Mirena - IUD
100
Which POCs are third line?
Jaydess - use if woman wants period or is having issues with Mirena
101
What are the advantages and disadvantages of the contraceptive injection?
Adv: lasts 8-13 weeks and may reduce heavy, painful periods
Disadv: fertility may take time to come back
102
What are the advantages and disadvantages of the implant?
Adv: works for 3 years, fertility and period go back to normal
Disadv: small procedure to fit and remove
103
What are the advantages and disadvantages of the intrauterine system?
Adv: 3-5 years depending on type and fertility goes back to normal on removal
Disadv: irregular bleeding/spotting in first 6 months and some can get ovarian cysts
104
What are the advantages and disadvantages of the intrauterine device?
Adv: 5-10 years and fertility return to normal
Disadv: period may be heavier or longer and more painful
105
What are the procedures for female sterilisation?
Fallopian tubes are cut, seals or blocked
106
What are the advantages and disadvantages of female sterilisation?
Adv: periods are unaffected and it can't easily be reversed
Disadv: other contraceptives until procedure is effective and there is a risk of ectopic pregnancy if sterilisation fails
107
What are the procedures for male sterilisation?
Vas deferent are cut, sealed or tied
108
What is a disadvantage of male sterilisation?
Need to use contraceptive until a semen tests show that there are no sperm left and this can take up to 8 weeks.
109
Define precocious puberty
Gives <8 years old who have started menstruation
110
What is primary dysmenorrhoea?
Cramping, pain to thighs and back with GI symptoms, headaches, fatigue/faintness
Peak incidence in teens to 20s
111
What is secondary dysmenorrhoea?
Consequence of other pelvic pathology. Pain may begin before menstruation.
Peak incidence in 30s - 40s
112
Describe the cause of primary dysmenorrhoea
Higher concentrations of prostaglandin in menstrual fluid
Increased myometrial contractility
Other mediators
- endothelins: vasoactive peptides regulate synthesis of prostaglandin
- vasopressin: stimulates uterine activity and decreases uterine blood flow
113
Pharmacological management of primary dysmenorrhea
```
NSAIDs
OTC: Feminax
POM: naproxen, mefanamic acid
Oral contraceptives
Antispasmodics
```
114
Describe the cause of secondary dysmenorrhea
```
Prostaglandin involvement
Underlying pelvic pathology
- PID
- endometriosis
- fibroids
- uterine polyps
```
115
Pharmacological management of secondary dysmenorrhea
Surgery: ablation or laser therapy
Symptomatic relief
Non analgesic treatment
116
Describe the causes of endometriosis
Development at embryological stage
Retrograde menstruation
Reflux menstrual loss
Increased prevalence with outflow obstruction
117
Describe the symptoms of endometriosis
```
Pain
Fatigue
Subfertility
Dyspareuria
Dyschezia
Dysurria
Chronic pelvic pain
Menstrual irregularities
```
118
How is endometriosis diagnosed?
Pelvic exam
Pelvic ultrasound
Diagnostic laparoscopy
119
What are the grades of endometriosis?
Grades 1-2
Minimal-mild, poorly visualised on ultrasound. Uterine and ovarian implantation
Grades 3-4
Moderate-severe, commonly associated with adhesions.
Rectovagincal endometriosis and bowel invasion
120
What are the aims of surgery in the treatment of endometriosis?
Restore normal pelvic anatomy, divide adhesions and ablate endometrial tissue
121
What are the aims of medicinal treatment in endometriosis?
| Give examples
Provide symptomatic relief and improve fertility
```
1st line: NSAIDs
2nd line: 'shrinkers'
Contraceptives
Progestogens or antiprogestogens
GnRH
SARMs - selective androgen receptos
Modulators - target biosynthetic pathways
```
122
Describe the potential causes of menorrhagia
```
Dysfunctional uterine bleeding (DUB)
Menopause, fibroids, PID, miscarriage/ectopic pregnancy, IUD, adenomyosis
Hepatic, renal or thyroid disease
PCOS
Blood thinning medication
```
123
Define menorrhagia
Menstrual blood loss >80ml per month
124
What are the symptoms of menorrhagia?
```
Irregular disease
Sudden change in blood loss
Intramentrual bleeding
Dyspareuria
Pelvic pain
Pre-menstrual pain
```
125
How is menorrhagia diagnosed?
```
Blood tests
Cervical smear
Biopsy
Ultrasound
Sonohysterography
Hysteroscopy
```
126
How is menorrhagia managed?
If contraception is required: CHC, POC, IUS/pararenteral progesterone
If contraception is not required: trxnexamic acid
Mefanamic acid
Oral progestogen: norethisterone
Antiprogestogens: Gestrinone / danazol
