Causes Of Infertility Flashcards
(196 cards)
1
Q
The likelihood that a couple will suffer from infertility is increased by several etiologic factors that may be physiological or non-physiological and that may impact both the male and/or the female partner including the following:
A
- age
- sexually transmitted disease
- lifestyle factors such as exercise, diet and drug intake
- environmental or occupational factors.
2
Q
The incidence and causes of infertility are likely to vary among populations studied, making exact numbers difficult to establish. One study of over 700 couples complaining of infertility suggested a number of causes, including
A
female factors in almost half of all cases and male factors in at least a quarter
3
Q
The hypothalamic-pituitary-ovarian axis is described above and is a complex system reliant on
A
feedback loops and stimulatory mechanisms that must be carefully controlled for proper function and regular ovulatory menstrual cycles to occur.
4
Q
An understanding of the mechanisms involved in bringing about ovulation is vital to
A
the understanding and treatment of infertility and in particular to restoring normal ovarian function.
5
Q
Age: There is a marked decline in a woman’s fertility that is directly attributable to her age long before she reaches menopause. This decline is
A
steady, age-related, and due to declining oocyte quality and number of primordial follicles
6
Q
Women < 25 years old are estimated to suffer from infertility at a rate of only
A
6%.
7
Q
Women aged > 40 years have a prevalence of infertility
A
> 60%
8
Q
Changes in menstrual cycle regularity as a woman nears menopause are preceded by
A
subtle changes in serum gonadotropins that can be the first indication of decreasing ovarian reserve and therefore declining oocyte quality.
9
Q
While elevated _____________________ are indicative of ovarian failure, normal FSH levels have little prognostic value.
A
follicular gonadotropins
10
Q
The consequences of abnormal FSH and/or E2 levels are a significantly lower chance of
A
pregnancy either naturally or with assisted reproduction.
11
Q
In addition, decreased ovarian reserve will require more aggressive use of gonadotropins in a stimulated cycle and is predictive of
A
lower pregnancy rates after IVF regardless of the patient’s age.
12
Q
Declining oocyte quality with maternal age is manifest in many ways including the following:
A
- degradation of the meiotic spindle
- nondisjunction and predivision of sister chromatids in oocytes
- increased incidence of aneuploidy in embryos
- higher cancellation rates and lower implantation rates after IVF
13
Q
Treating infertility due to maternal age is difficult and live birth rates even after aggressive IVF treatment remain low. Controversy exists as to whether transferring high numbers of embryos in older patients is beneficial. _________________ can be used to select embryos for transfer leading to a shorter time to pregnancy after IVF.
A
PGT-A
14
Q
Women over the age of 35 should be advised to begin aggressive fertility treatments such as IVF since protracted investigation of their infertility may cost them valuable time. For women over 40, IVF success rates are extremely low due to
A
reduced ability to recruit oocytes during ovarian hyperstimulation and low quality of any oocytes that are recruited.
15
Q
_____________________ remains the fastest and most reliable way for treating advanced maternal age and carries the highest success rate of any infertility therapy for these women.
A
Donor oocyte
16
Q
Disorders of Ovulation:
A
- Oligomenorrhea (irregular ovulation)
- amenorrhea (failure to ovulate)
17
Q
Disorders of ovulation account for infertility in about _______% of cases.
A
20
18
Q
Confirmation of the regularity and length of a woman’s menstrual cycles is important since normal cycles almost certainly include
A
ovulation.
19
Q
This can be confirmed clinically by a simple (but seldom used) test to measure
A
serum progesterone level 7 days following ovulation.
20
Q
Normal levels of progesterone 7 days after ovulation indicate a
A
normal follicular phase and ovulation, as well as a functioning luteal phase in the cycle.
21
Q
In cases of correctable hormone disturbances, it may be reasonable to withhold IVF treatment in young women, if
A
her partner has a normal semen analysis.
22
Q
Ovulation failure may result from:
A
- primary amenorrhea
- secondary amenorrhea
- secondary dysmenorrhea
- Delayed menstruation
23
Q
Primary amenorrhea
A
absence of menses/onset of menarche a female > 15 years of age
24
Q
Secondary amenorrhea
A
no menstruation for > 3 months in a female with previous regular menstrual cycles or >6 months in a female with previously irregular cycles
25
Secondary dysmenorrhea
menstruation may be associated with recurrent lower abdominal pain that results from an underlying condition such as endometriosis.
26
Delayed menstruation
in non-pregnant women who are not using birth control may result from hormonal imbalances (such as those seen in women with polycystic ovarian syndrome, stress, fluctuating weight, perimenopause, or serious medical condition such as diabetes, thyroid disease, a pituitary tumor, or other cancers.
27
Uterine factors: Uterine infertility is difficult to define due to the uncertain influence of physical abnormalities on implantation. These are usually picked up with the use of
ultrasound, hysteroscopy, and/or hysterosalpingogram (HSG) and include polyps, fibroids, synechiae, intrauterine adhesions, leiomyomata (myomas).
27
Myomas, polyps, or fibroids develop at various times during the
reproductive lifespan and are benign growths in the smooth muscle of the uterine wall.
28
They are poorly characterized both in origin and impact on fertility but large and or numerous growths are likely to
interfere with uterine function, implantation, or maintenance of a pregnancy.
29
30
Myomectomy, or removal of these growths, can be accomplished hysteroscopically if they are < 3 cm in size, but __________________ or __________________ would be required for the larger growths.
laparoscopy or laparotomy
31
32
Congenital müllerian abnormalities (errors during fetal development) such as septate
unicornuate, and T-shaped uterus, or a rudimentary uterine horn arise from the absence or incomplete fusion of
33
34
the uterine horns (unicornuate, bicornuate), a more caudal fusion defect (septa), or incomplete resorption of the fusion line
35
Drug exposure during pregnancy (e.g. diethylstilbestrol (DES) and
36
and thalidomide) can also cause these abnormalities in the genital tract. A full review of these and
37
other uterine abnormalities is given in Sims and Gibbons
1996. Treating underlying gynecological
38
disease with medical or surgical interventions would be one approach and considered the optimal
39
current therapy by some practitioners. In most instances
how treatment proceeds is considered on
40
an individual basis.
41
. Cervical infertility: Several measures of cervical mucus functionality are used
including ferning
42
pattern when dried on a glass slide
stretchability (known as spinnbarkeit)
43
Absence of these properties at midcycle may be due to low Ez or iatrogenic damage to the cervix
44
resulting from ablative
cryo
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infection
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sperm immobilizing antibodies that reside there
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insufficient E2
48
low mucus volume
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Normal mucus and the crypts that produce it act as a sperm reservoir after intercourse allowing
50
waves of spermatozoa into the uterus (Moghissi
1976). The controversial post-coital test (Huehner
51
test) looks at sperm quantity and penetration in the hours immediately following intercourse. The
52
Insler SCore the measure of sperm numbers and performance in the mucus
and a score of 5 or
53
more sperm per high power field with forward motility is considered normal. This test should not be
54
confused with the sperm-mucus assay or Kremer test that measures sperm penetration into human
55
or bovine mucus in the laboratory. The Kremer test can be used to detect antibodies to sperm that
56
may result from sperm access to maternal blood stream. These antibodies are difficult to test for but
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are believed to be present in 10%-15% of women with unexplained infertility (Edwards and Brody
58
1995). Patients presenting with abnormal mucus or mucus production problems are offered IUI or IVF
59
as a therapy to overcome (bypass) the hostile cervix.
60
Tubal disease: The fallopian tube is the site of fertilization
and transport of the ovum and
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spermatozoa to each other requires patent and functional tubes. Transport is affected by various
62
conditions such as endometriosis
pelvic inflammatory disease
63
Chlamydia infection
for example
64
US and can be sub-clinical but still destroy the tubes. Blockages with trapped fluid accumulating are
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called hydrosalpinx and these are associated with lower pregnancy rates after assisted
66
reproduction. One report suggested that the pregnancy rate is only 10% if they are larger than 2.5 cm
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growths are likely to interfere with uterine function
implantation
67
VIl.
68
Myomectomy
or removal of these growths
68
IX.
69
cm in size
but laparoscopy or laparotomy would be required for the larger growths. Congenital
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X
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(Vandromme et al.
1985). Treatment for damaged or non-functional tubes varies but if only one tube
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müllerian abnormalities (errors during fetal development) such as septate
unicornuate
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is blocked
removing that ovary and allowing the other ovary to ovulate every month can enhance
71
and T-shaped uterus
or a rudimentary uterine horn arise from the absence or incomplete fusion of
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fertility. The removal of hydrosalpinges is often accompanied by the removal of the entire tube
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the uterine horns (unicornuate
bicornuate)
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(salpingectomy) to prevent the occurrence of ectopic (extra-uterine) pregnancies. Younger patients
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resorption of the fusion line (septate). Drug exposure during pregnancy (e.g.
diethylstilbestrol (DES)
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might consider tubal reconstruction if the damage is minimal and other infertility issues do not exist.
74
and thalidomide) can also cause these abnormalities in the genital tract. A full review of these and
75
After fallopian tube removal
IVF is the only path to fertility
75
other uterine abnormalities is given in Sims and Gibbons
1996. Treating underlying gynecological
76
patients
76
disease with medical or surgical interventions would be one approach and considered the optimal
77
Polycystic ovary disease/syndrome: When upwards of 15 small cysts or follicles are visualized in a
77
current therapy by some practitioners. In most instances
how treatment proceeds is considered on
78
single ovarian plane with vaginal ultrasound
the term polycystic ovaries (PCO) comes into play.
78
an individual basis.
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Common in apparently normal women
PCO is associated with ovarian enlargement and is the
79
. Cervical infertility: Several measures of cervical mucus functionality are used
including ferning
80
commonest cause of anovulation (Polson et al.
1988). The syndrome (PCOS) is assigned to women
80
pattern when dried on a glass slide
stretchability (known as spinnbarkeit)
81
with anovulation
as well as hyperandrogenism and an elevated LH/FSH ratio. Patients with PCO
81
Absence of these properties at midcycle may be due to low Ez or iatrogenic damage to the cervix
82
have an excessive response to ovarian stimulation during fertility treatments but otherwise good
82
resulting from ablative
cryo
83
outcomes when superovulation proceeds cautiously
with low dose gonadotropin therapy and
83
infection
84
increased frequency of monitoring.
84
sperm immobilizing antibodies that reside there
85
Endometriosis: When endometrial tissue migrates or appears in extra-uterine locations the patient is
85
insufficient E2
86
suffering from endometriosis. Endometriosis is more common in infertile women when compared to
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low mucus volume
87
fertile women and it causes the following symptoms:
87
Normal mucus and the crypts that produce it act as a sperm reservoir after intercourse allowing
88
> pain
88
waves of spermatozoa into the uterus (Moghissi
1976). The controversial post-coital test (Huehner
89
infertility
89
test) looks at sperm quantity and penetration in the hours immediately following intercourse. The
90
adhesions
90
Insler SCore the measure of sperm numbers and performance in the mucus
and a score of 5 or
91
dysfunctional menstrual cycles
91
more sperm per high power field with forward motility is considered normal. This test should not be
92
> interference with gamete transport and fertilization
92
confused with the sperm-mucus assay or Kremer test that measures sperm penetration into human
93
Controversy exists as to its effects on oocyte quality and implantation. This disease feeds off
93
or bovine mucus in the laboratory. The Kremer test can be used to detect antibodies to sperm that
94
gonadotropins and Ez
since these stimulate endometrial growth. Drugs that interfere with
94
may result from sperm access to maternal blood stream. These antibodies are difficult to test for but
95
gonadotropin output such as gonadotropin releasing hormone agonists are useful but may place
95
are believed to be present in 10%-15% of women with unexplained infertility (Edwards and Brody
96
the patient in a temporary menopausal state
thus preventing her from geting pregnant. Surgical
96
1995). Patients presenting with abnormal mucus or mucus production problems are offered IUI or IVF
97
ablation of the lesions combined with the agonist therapy helps avoid recurrence. IVF is an effective
97
as a therapy to overcome (bypass) the hostile cervix.
98
therapy for getting these patients pregnant
but implantation rates may be reduced by the severity of
98
Tubal disease: The fallopian tube is the site of fertilization
and transport of the ovum and
99
the disease.
99
spermatozoa to each other requires patent and functional tubes. Transport is affected by various
100
Diminished ovarian reserve (DOR) is a limiting factor for both female fertility and the success of
100
conditions such as endometriosis
pelvic inflammatory disease
101
infertility treatments. DOR is poorly defined
likely due to it resulting from variable causes
101
Chlamydia infection
for example
102
generally seen as a phenomenon affecting women in their mid to late thirties
although younger
102
US and can be sub-clinical but still destroy the tubes. Blockages with trapped fluid accumulating are
103
women may also present with DOR. It is believed to arise due to an accelerated decline in the size
103
called hydrosalpinx and these are associated with lower pregnancy rates after assisted
104
of the follicle reserve. There is thus a limited time for a woman to conceive with her own eggs. There
104
reproduction. One report suggested that the pregnancy rate is only 10% if they are larger than 2.5 cm
105
may also be an associated decline in oocyte quality due to aging oocytes that impacts women of al
106
ages with DOR (E-Toukhy et al.
2002).
107
XI.
108
XII.
109
DOR is normally associated with advanced female (maternal) age (AMA)
but other factors
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proposed to cause an accelerated decline in ovarian reserve include the following:
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a difference in the initial size or the rate of depletion of the primordial folicle pool between
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different women
113
endomtrioma
certain pelvic infections and ovarian surgery that may impact ovarian
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endocrinology and other regulatory mechanisms
115
ethnicity
116
altered expression of certain genes in follicular cells.
117
Advanced female and male age have been associated with an increased risk of disease in the
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offspring such as monogenetic diseases
as well as conditions that are manifest in adulthood
119
(examples include cancers
autism
120
Recurrent pregnancy Loss (RPL): The American Society of Reproductive Medicine (ASRM)
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practice committee defined RPL as "a disease distinct from infertility
defined by two or more failed
122
pregnancies
" where pregnancy was confirmed by ultrasound (Practice Committee of ASRM, 2013).
RPL İs reported to affect about 1%-2% of women when defined as three pregnancy losses prior to 20
weeks from the last menstrual period. Diagnosis of RPL is further complicated by an overall
pregnancy loss rate of around 15% in the general population, lack of consistent definition, limited
access to tissues allowing study of the disorder and the long-term good prognosis for live birth among
RPL patients.
Recognized causes of RPL include parental chromosomal abnormalities, untreated
hypothyroidism, uncontrolled diabetes mellitus, certain uterine anatomic abnormalities, and
antiphospholipid antibody syndrome (APS).
Probable causes include other endocrine disorders, heritable and/or acquired thrombophilias,
immunologic abnormalities, infections, and environmental factors.
These patients should use a therapeutic approach directed toward treatable etiologies, such as
correction of endocrine disorders and surgical correction of anatomic abnormalities. Other
approaches may include IVF with PGT-A, use of donor gametes, anticoagulation, and folic acid
supplementation (Ford and Schust, 2009). However, approximately 50% of RPL patients will have no
associated explanation for their continued pregnancy losses, and therapeutic options are limited.
Progesterone support has been shown to be beneficial in decreasing pregnancy loss in this
population of patients, as weil as low-dose aspirin.
Cancer, chemotherapy and infertility: Survival after cancer treatment increasing steadily with
approximately 75% of individuals under the age of 45 having to address the impact of their disease
on future lifestyle choices such as fertility. Surgery, chemotherapy, and radiation used to treat cancer
can affect infertility by impacting the neuroendocrine axis, immature and growing follicles, and
reproductive organs necessary for pregnancy. Moreover, the risk of infertility varies for different age
groups and different cancer treatments, and it is now evident that cancer survivors treated with pelvic
radiation or ankylating chemotherapy agents will experience premature menopause. The disease
123
XIII.
124
itself may impact ovarian response to stimulation regimes leading to an unexpected poor response
125
and few o0cytes
or a prolonged and costly period of high doses of gonadotropins needed to obtain
126
sufficient growing follicles to proceed with oocyte retrieval. Oocyte quality may also be p0or.
127
Many women experience transient or longterm amenorrhea and where possible fertility
128
preservation prior to cancer treatment should be considered (Waimey et al.
2015). Embryo
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cryopreservation for patients with a partner is most associated with future fertility success. Oocyte
130
cryopreservation can offer a standard means of gamete preservation
although any potential impact
131
of the disease on oocyte function will not be apparent until after cancer treatment
when the patient
132
chooses to fertilize her eggs. Ovarian tissue cryopreservation can be offered to patients whose
133
cancer treatment is imminent and cannot be delayed for ovarian stimulation or for whom ovarian
134
stimulation is contraindicated. This investigational technique has resulted in about 100 live births to
135
date
after re-implanting thawed ovarian tissue
136
cancer for whom tissue transfer may re-seed the original cancer. Gamete donation remains an
137
option for this group of patients
providing there is no damage to the uterine structure or function.
138
Unexplained (idiopathic) infertility: A significant number of women never find the cause of their
139
infertility
although this is partially due to insufficient testing or investigation on the part of the
140
physician. Many times
and particularly with advanced maternal age
141
forego further testing in favor of treatment that might bring resolution to the patient's infertility. The
142
chance to proceed with intra uterine insemination (lU) or IVF therapy and have an oppotunity for
143
pregnancy may seem more appealing to patient and doctor alike in preference to months of continued
144
testing. For women with true unexplained infertility
there may be subtle sub-clinical factors or a
145
combination of factors that prevent pregnancy. For example
there is conflicting evidence in the
146
literature that smoking contributes to infertility
and certainly its effects on a given couple's fertility
147
would be difficult to determine.
148
C. Summary
149
The investigation and treatment of the cause(s) of infertility are complex and vast. Fortunately
the
150
disease is resolved in many patients with the use of assisted reproduction technologies. Couples
151
presenting with infertility after 12 months of frequent and timed intercourse can benefit from modern
152
treatments and technology. Age is the single most important factor in a woman's ability to conceive and
153
infertility testing can sometimes be bypassed in favor of aggressive treatments in older patients. Infertility
154
testing can be extensive and expensive and the possibility of pregnancy with reproductive assistance is
155
often more appealing than further investigations. However
while IVF has resolved infertility problems for
156
many individuals since its introduction
not all patients will succeed with a viable pregnancy after VE.
157
Patients should be given a realistic prognosis before embarking on treatment.
