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Objective: To assess the correlation between low levels of progesterone and ovulation by ultrasound monitoring in infertile patients with regular menstrual cycles. Methods: Case-control study. The sample consisted of 302 women aged 20-40 years, treated from 2000 to 2014 in the Human Reproduction Laboratory of the University Hospital of the Federal University of Goiás and in the Department of Gynecology and Obstetrics in Goiânia, Goiás. Data collection was performed by analysis of physical records (Medical Records and Health Information Services) and electronic ones (Sisfert©, 2004) after approval by a Human Research Ethics Committee. Patients were classified according to their ovulatory status, evaluated by progesterone levels and ultrasound monitoring and divided into two groups: Group I (anovulatory cycle patients, n=74) and Group II (ovulatory patients, n=228). In both groups associations were made between the percentage of patients with normal progesterone (≥ 10 ng/ml) and percentage of patients with low progesterone (5.65 - 9.9 ng/ml). The groups were paired for comparisons related to age, body mass index, duration of infertility, follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), luteinizing hormone (LH) and estradiol (E2). Results: There was a significant association between the percentage of ovulation by ultrasound monitoring and the percentages of patients who presented low levels of progesterone. Conclusion: The study suggests that low serum levels of progesterone are associated with low percentage of ovulation in infertile women with regular menstrual cycles and women with unexplained infertility.
Original Article
Low progesterone levels and ovulation by ultrasound assessment
in infertile patients
Eliane G. M. Sanchez1, Christiane R. Giviziez1, Hugo M. Sanchez1, Patrícia L. S. Agostinho1, Patrícia S. Barros1,
Mário S. Approbato2
1Federal University of Goiás. Medical School. University Hospital. Gynecology and Obstetrics Department.
Human Reproduction Lab - Goiânia (GO) - Brazil
2Federal University of Goiás – Jataí (GO) - Brazil
Objective: To assess the correlation between low levels
of progesterone and ovulation by ultrasound monitoring in
infertile patients with regular menstrual cycles.
Methods: Case-control study. The sample consisted of
302 women aged 20-40 years, treated from 2000 to 2014
in the Human Reproduction Laboratory of the University
Hospital of the Federal University of Goiás and in the De-
partment of Gynecology and Obstetrics in Goiânia, Goiás.
Data collection was performed by analysis of physical re-
cords (Medical Records and Health Information Services)
and electronic ones (Sisfert©, 2004) after approval by a
Human Research Ethics Committee. Patients were clas-
sied according to their ovulatory status, evaluated by
progesterone levels and ultrasound monitoring and divid-
ed into two groups: Group I (anovulatory cycle patients,
n=74) and Group II (ovulatory patients, n=228). In both
groups associations were made between the percentage
of patients with normal progesterone (≥ 10 ng/ml) and
percentage of patients with low progesterone (5.65 - 9.9
ng/ml). The groups were paired for comparisons related to
age, body mass index, duration of infertility, follicle stimu-
lating hormone (FSH), thyroid stimulating hormone (TSH),
luteinizing hormone (LH) and estradiol (E2).
Results: There was a signicant association between the
percentage of ovulation by ultrasound monitoring and the
percentages of patients who presented low levels of pro-
Conclusions: The study suggests that low serum levels of
progesterone are associated with low percentage of ovula-
tion in infertile women with regular menstrual cycles and
women with unexplained infertility.
Keywords: Infertility, Ovulation, Regular cycles, Low pro-
The World Health Organization (WHO) denes infertility
as the absence of pregnancy after one year or more of sexual
relations with no use of contraceptives (Rowe et al., 1993).
It is estimated that there are from 50 to 80 million
infertile couples in the world, with about two million
new cases per year (Gonçalves, 2005). This event is ex-
perienced by 8-15% of couples in general. In Brazil,
more than 278,000 couples have some difculty in con-
ceiving a child at some point in their childbearing age.
The causes of infertility in women could be due to
anatomical factors related to the uterus or the fallopian
tubes; hormonal causes that affect the hypothalamic-pi-
tuitary-ovarian axis; and sterility without apparent cause
(ESCA). It is believed that these factors correspond to 35%
of infertility causes in women, 35% in men; 20% are asso-
ciated with female and male issues, and 10% with ESCA.
Ovulatory dysfunctions represent the main causes
of female infertility, accounting for up to 40% of them
(ASRM, 2012). Among the causes, hormonal changes
are the most important, especially for infertility. Among
them, we can highlight Polycystic Ovarian Syndrome
(PCOS), hypothyroidism, hyperprolactinemia, low levels
of progesterone (P4), among others (McLaren, 2012).
Progesterone (P4) is a hormone produced after puberty,
by the corpus luteum (CL) and by the placenta during the
pregnancy and it acts in the regulation of normal female re-
productive functions. The endometrium is prepared In the
womb, facilitating deployment and maintenance of early
pregnancy (Al-Asmakh, 2007). For this reason P4 plays a
vital role in female fertility and low levels of it can signi-
cantly decrease the chances of pregnancy due the proba-
ble inuence on endometrial development (ASRM, 2015).
P4 was rst associated with the corpus luteum by the
huge production of this steroid after ovulation. Currently, it
is known that its secretion starts from the moment a ma-
ture ovarian follicle is stimulated by LH release (Ke, 2014;
Moreira, 2014).
According to the ASRM (2012), ovulatory function can
be evaluated by assessing P4 levels in the bloodstream, but
it should be obtained at appropriate times in the menstrual
It is usually recommended that P4 be dosed from 7 to
9 days after the suspected ovulation. Some authors con-
sider this event to happen with P4 levels starting at 3ng/
ml (Guttmacher et al., 1956; Garzia et al., 2004; ASRM,
2012; McLaren, 2012). The World Health Organization
(Rowe et al., 1993) stresses ovulatory P4 levels ≥ 5.65 ng/
ml, measured between the 20th and 24th days of a 28-day
cycle. Serum progesterone levels higher than 10 ng/ml are
used as a parameter to measure ovulatory function by the
ASRM (2012).
P4 levels may suffer discrete increases and cause the
non-rupture of a luteinized follicle (LUF). In this event, the
follicle develops itself normally, grows and matures, but
does not break to release the ovum; however, there may
be a P4 secretion, such as a follicle that brakes, originating
the CL. Thus, there is no ovulation, but the follicle secretes
P4, making serum levels increase slightly. In this case, val-
ues don’t reach the 10 ng/ml and it establishes a low level
of P4 (Van Zonneveld et al., 1994) causing anovulation.
Low P4 is one of the causes of anovulation and
a subtle cause of female infertility (Young & Lessey,
2010), which can be characterized by insufcient P4 se-
cretion to maintain the endometrium, preventing im-
plantation and normal embryo growth (Sonntag &
Ludwig 2012; Schliep, 2014). It can be found by P4
dosing and through invasive procedures or sophisticat-
ed ovulation assessment equipment (Mardesic, 1990).
There’s no standard characterization yet to evaluate
progesterone secretion during the luteal phase in nor-
mal fertile women and there is no established minimum
P4 value to determine an adequate luteal function. Fur-
thermore, it is known that the corpus luteum function var-
JBRA Assisted Reproduction 2016;20(1):13-16
doi: 10.5935/1518-0557.20160004
Received September 28, 2015
Accepted December 30, 2015 13
Original Article 14
Table 1. Distribution of patients according to LUF and Non-LUF groups comparison (confounding variables).
HC-UFG / Mater Clinic, Goiania 2000-2014.
General features LUF (n=74) Non-LUF (n=228) P
Age 31.54±4.71 31.85±4.21 0.32
BMI 24.83±3.85 23.88±3.93 0.07
LH 4.56±6.51 4.61±2.74 0.06
FSH 6.26±1.45 5.98±1.68 0.07
TSH 2.50±0.93 2.16±1.19 0.75
Estradiol (E2) 51.84±35.82 54.34±51.09 0.12
Infertility duration 67.61±47.81 64.17±46.95 0.28
BMI (Body Mass Index); LH (luteinizing hormone) FSH (Follicle Stimulating Hormone); TSH (thyroid-stimulating hormone)
ies from cycle to cycle, but if properly collected, serum
progesterone levels can be useful in clinical diagnosis to
assess the adequacy of the luteal phase (ASRM, 2015).
Some authors suggest that the diagnosis of decreased
P4 can be done by levels <10 ng/ml (Van Zonneveld et
al., 1994), others indicate values <8 ng/ml (Litwack &
Begley, 2001); and Arce et al. (2011) suggest values be-
tween 7.9 - 10 ng/ml may indicate LUF. Although there
is certain proximity between P4 values indicative of LUF,
there is still no consensus about low P4 threshold levels.
The identication of anovulatory cycles is a challenge
for healthcare professionals. Ovulation prediction or conr-
mation may also be obtained by serial monitoring through
transvaginal ultrasound, to measure follicle growth and
allow the evaluation of follicular rupture (ASRM, 2012).
Transvaginal US is of the gold standard for ovulation di-
agnosis during the menstrual cycle, but difcult to be used
in epidemiological studies. In the absence of this method,
measurements of concentrations of reproductive hormones
are commonly used to identify the ovulatory status in re-
search, among them the measure of P4 levels stands out.
A combination of methods for measuring ovulation
has been recommended in order to obtain a more accu-
rate diagnosis. The Labrep (Human Reproduction Labora-
tory) HC/UFG (University Hospital of the Federal Univer-
sity of Goiás) associates monitoring of ovarian follicles
through ultrasound and the dosage of P4 serum levels
to diagnose ovulation, although women with low P4 are
not necessarily submitted to ultrasound check, which
may be responsible for inconsistent ovulatory diagnos-
tics. This study is justied by the lack of literature show-
ing the low progesterone inuence in the ovulation of in-
fertile women with regular cycles. Thus, the aim of this
study was to evaluate the association between low levels
of P4 and US ovulation assessment in infertile patients
with regular cycles suffering from unexplained infertility.
This is a case-control study. There were 302 patients
selected, aged between 20 and 40 years, seen between
2000 and 2014 in the Human Reproduction Laborato-
ry of the University Hospital of the Federal University of
Goiás/UFG and in the Clinic of Gynecology and Obstet-
rics of the private healthcare network in Goiania – Goias.
Data was collected from the medical charts
stored in the Medical Ofce Management Sys-
tem (SAMIS) and from the electronic charts from
the Sisfert© database, which started after approv-
al by the Human Research Ethics Committee HC/UFG.
Women who had been evaluated by ultrasound and had
presented both regular progesterone levels and ovulatory
cycles were included; women with FSH levels above 9.9
mIU/mL (basal FSH = 1.4 to 9.9 mIU/mL) were exclud-
ed, as were those with TSH higher than 4.7 (basal = 0,
4 and 5 mIU/L) (Garber et al., 2012), those with Poly-
cystic Ovarian Syndrome with oligomenorrhea or amen-
orrhea, users of medicines that would interfere with ovu-
lation and women under 20 and over 40 years of age.
The patients were broken down into two groups ac-
cording to their ovulatory state determined by transvag-
inal ultrasound monitoring: Group I (n=74) anovulatory,
comprising women who had P4 levels of 5.65 - 9.9 ng/ml
and lack of follicular collapse - evaluated by monitoring
with intravaginal US. Group II (n=228) ovulatory, consist-
ed of women with P4 levels ≥10 ng/mL and follicular col-
lapse evaluated by monitoring through US (ASRM, 2012).
Among those groups, two groups were evaluated to obtain
the percentage of patients with normal ovulatory proges-
terone (≥10 ng/mL) and the percentage of patients with
low progesterone (5.65 to 9.9 ng/mL) considered as LUF
in the study. Those groups were paired for comparison in
relation to age, body mass index, infertility duration, Folli-
cle Stimulating Hormone - FSH (ng/mL), Thyroid-stimulat-
ing Hormone - TSH (mIU/mL), Luteinizing Hormone - LH
(mIU/mL) Estradiol (E2) (pg/mL), according to Table 1.
The statistical analysis was performed using IBM
SPSS Statistics 20.0 (Statistical Packages for Social Sci-
ences, USA) and the Bioestat (version 5.3). We used the
Chi-square test with a condence interval of 95% and
P =0.05 for signicance level. Where the statistical anal-
JBRA Assist. Reprod. | V.20 | no1| Jan-Feb-Mar/ 2016
Table 2. Distribution of the second ovulation according to patients’ P4 levels (normal and 5.65 -9.9 ngml) from the
LabRep HC - UFG / Mater Clinic. Goiania, 2000-2014.
LUF (P4) Ovulation
Total X2P
Group I (LUF) 50 (20.4%) 24 (42.1%) 74 11.76 0.001
Group II (No LUF) 195 (79.6%) 33 (57.9%) 228
Total 245 57 302
P4 (progesterone); X2 (chi-square value). Group I - LUF (P4 5.65 - 9.9 ng/ml); Group II - No LUF (P4 ≥ 10 ng/ml). IC
95% (0.191 - 0.649). OR (odds ratio) = 0.353
Low levels of progesterone and ovulation - Sanchez, E 15
JBRA Assist. Reprod. | V.20 | no1| Jan-Feb-Mar/ 2016
ysis was not performed, we calculated the mean value
and the standard deviation of the variables under study.
The results obtained are presented in tables as fol-
lows. The comparability of the two populations stud-
ied is shown on Table 1. Comparability tests did not
show statistically signicant differences (P>0.05).
Table 2 shows a signicant association between the
percentage of ovulation through ultrasound and the per-
centage of patients who had low progesterone levels
(OR=0.353); IC (95%): 0.191 – 0.649. P=0.001.
This study has shown that low P4 levels are associ-
ated with signicant decreases in ovulation in infertile
women with regular cycles, women with unexplained
infertility. This fact was explained by Mesen & Young
(2015) when they reported that a defected luteal phase
may decrease P4 levels and the fertility in women.
It’s interesting to highlight that, despite the pul-
satile release of P4, its low levels on a single measure-
ment may not always indicate ovulatory disorders (ASRM,
2012). On the other hand, this present study found
ovulatory changes conrmed by monitoring through ul-
trasound in 42.1% of women who presented low P4.
Studies which evaluate P4 values in women with regular
cycles are unusual (Fatemi, 2009; Young & Lessey, 2010).
This study evaluated P4 levels in this group of women.
While normal P4 values are related to regular cycles and
ovulation, lower values may reect the presence of unrup-
tured luteinized follicle (LUF) (Schliep, 2014). In a study by
Litwack & Begley (2001) the ovulatory status was evaluat-
ed considering the P4 levels for three menstrual cycles in
543 patients with infertility history longer than two years.
From the population studied so far, 461 (90.2%) had nor-
mal ovulatory cycles conrmed by ultrasound monitoring
and 50 (9.8%) had anovulatory cycles. In this study, val-
ues considered suggestive of ovulation were the ones with
P4 levels > 8ng/ml, and P4 levels <8 ng/mL were con-
sidered low values. Out of the population being studied,
292 women (63.9%) had normal P4 and 165 (36.1%) had
low P4. From the group with apparently normal P4 values,
7.2% of women got pregnant when compared to 3.6% of
women with low P4. Our study showed signicant reduc-
tion (P <0.001) in the fertility of patients with low proges-
terone levels. It also corroborates the study by Hamilton et
al. (1987), who evaluated 201 ovulatory cycles in 170 in-
fertile women by measuring ovarian follicles through ultra-
sound and P4 levels. In our study we found LUF in 71% of
the cycles in which the P4 levels were lower than 10ng/ml,
and in 7.9% of cycles in which P4 levels were higher than
10ng/ml. These data corroborate the results of the present
study which also found LUF in cycles (20.4%) in which P4
levels were over 10ng/ml. Eissa et al. (1987) studied ovu-
latory cycles in 45 subfertile women and found LUF in 19%
of cycles, but neither reported P4 values used to determine
LUF, nor highlighted the monitoring of the ovulatory folli-
cle through US. The sensitivity and specicity of diagnostic
methods of ovulation were evaluated by Mesen & Young
(2015), wherein they found that P4 levels stand out among
other evaluating methods, including endometrial biopsy.
This study showed an association between an-
ovulation through ultrasound and low levels of P4.
This study suggests that low progesterone levels are
associated with a reduction in ovulation percentage in in-
fertile women with regular menstrual cycles and women
with unexplained infertility. The number (n) of women used
in the study favors greater emphasis on results found.
No conict of interest have been declared.
Corresponding author:
Eliane Gouveia de Morais Sanchez
Universidade Federal de Goiás. Faculdade de Medicina.
Departamento de Ginecologia e Obstetrícia. Hospital das
Laboratório de Reprodução Humana
Goiânia (GO) - Brasil.
E-mail: egm
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... Figure 4 illustrates the relationship between biomarkers of these three pathways and clinical outcomes. Obese women are at increased risk of subfertility which can be related to lower progesterone and increased leptin levels [40,177]. Leptin can modulate reproductive function by affecting ovarian folliculogenesis and ovulation, and by perturbing the hypothalamic-pituitary-gonadal axis, such as by lowering progesterone and gonadotropin-releasing hormone levels [178,179]. ...
Full-text available
Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity can unravel pathophysiologic mechanisms and identify individuals at risk of adverse clinical outcomes. The literature was systematically reviewed to identify periconceptional biomarkers of the endocrine, inflammatory and one-carbon metabolic pathways influenced by maternal obesity. A search was conducted in Embase, Ovid Medline All, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases, complemented by manual search in PubMed until December 31st, 2020. Eligible studies were those that measured biomarker(s) in relation to maternal obesity, overweight/obesity or body mass index (BMI) during the periconceptional period (14 weeks preconception until 14 weeks post conception). The ErasmusAGE score was used to assess the quality of included studies. Fifty-one articles were included that evaluated over 40 biomarkers. Endocrine biomarkers associated with maternal obesity included leptin, insulin, thyroid stimulating hormone, adiponectin, progesterone, free T4 and human chorionic gonadotropin. C-reactive protein was associated with obesity as part of the inflammatory pathway, while the associated one-carbon metabolism biomarkers were folate and vitamin B12. BMI was positively associated with leptin, C-reactive protein and insulin resistance, and negatively associated with Free T4, progesterone and human chorionic gonadotropin. Concerning the remaining studied biomarkers, strong conclusions could not be established due to limited or contradictory data. Future research should focus on determining the predictive value of the optimal set of biomarkers for their use in clinical settings. The most promising biomarkers include leptin, adiponectin, human chorionic gonadotropin, insulin, progesterone and CRP.
... After ovulation, progesterone is secreted, which prepares the endometrium for implantation. It is known that progesterone levels drop when implantation does not occur and corpus luteum regresses [38]; thus, a lower concentration of progesterone is associated with reduced ovulation in infertile females [36,44]. We have checked the association of estrogen concentration with fecundity and found no significant results. ...
Infertility affects 1 out of 6 couples of the world population and has multifactorial etiologies. The aim of the present study is to identify the correlation between some causative factors and female infertility. The detailed proforma with patient’s informed consent was filled out for total 120 females (42 control females and 78 case females, which included personal information, family history, lifestyle factors and serum hormone levels). Results showed that age, body mass index (BMI), previous history of miscarriage, and previous history of conception were significantly (p < 0.001) associated with female infertility. Similarly, independent t test results of clinical profile showed significant (p < 0.001) association of serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone, and anti-Mullerian hormone (AMH). There was a non-significant association of lifestyle factors (alcohol consumption, smoking, diet, caffeine consumption, and menstrual cycle regularity) and family history of consanguineous marriage with female infertility. Also, we have found a nonsignificant association between female infertility and complaint of infertility in other family members of probands. The present study confirms that these factors are important aspects for determining the etiology of female infertility and will further help in the management of disease and provide essential treatment if required.
... In our study, it was seen in 23.5% subjects as compared to a study by Ying Y K et al, it was seen in 15% cases. 12 Women with early conversion of endometrium as seen on ultrasound and serum progesterone levels of more than 1.5 ng/ml at dominant follicle of 18-20 mm found to have premature luteinization. Premature luteinization adversely affects clinical pregnancy rate probably due to embryoendometrial asynchrony. ...
Objective: The incidence of unexplained infertility is high and thus there is a need to assess usefulness of unexplored modalities i.e. ultrasonographic follicular monitoring and endometrial changes and its correlation with hormonal levels in spontaneous menstrual cycle. Our study aimed to detect subtle defects responsible for the same. Methodology: It was an observational study conducted in the infertility clinic of Lady Hardinge Medical College, New Delhi, India. Fifty women with unexplained infertility were included in the study. The subjects were called on day 2-3 of onset of menses for a baseline transvaginal ultrasound for antral follicular count, endometrial thickness and hormonal profile. Follow-up ultrasonographic monitoring was done till ovulation was documented. Hormonal profile was done on day of dominant follicle of 18-20 mm and on day 21, serum progesterone levels were done. Results: The mean age of study group was 26.48±3.3 years. Primary infertility was seen in 66% cases and secondary infertility in 34%. Seventy eight percent women had at least one or a combination of subtle defects in their monitored cycles. The mean antral follicle count was 13.8±5.17. Only one woman had antral follicle count of less than 5. 30% of women had levels of FSH more than 10 IU/L and levels of serum estradiol more than 80 pg/ml. Luteal phase defect and premature LH surge was seen in 34 % women each. Conclusion: Spontaneous cycle follicular monitoring is a useful tool to provide insight into the subtle defects like premature depletion of ovarian reserve, defective folliculogenesis, poor oocyte quality, premature luteinization, luteinized unruptured follicular syndrome contributing to unexplained infertility. Transvaginal sonographic assessment of a spontaneous cycle thus, appeared to be a useful addition in the investigative work-up of women with unexplained infertility.
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Context: Although adequate luteal hormone production is essential for establishing pregnancy, luteal phase deficiency (LPD) is poorly characterized among eumenorrheic women. Objective: We assessed the prevalence and overlap of two established LPD diagnostic criteria: short luteal phase duration less than10 days (clinical LPD) and suboptimal luteal progesterone of 5 ng/mL or less (biochemical LPD) and their relationship with reproductive hormone concentrations. Design, setting, and participants: We conducted a prospective study in western New York (2005-2007) following 259 women, aged 18-44 years, for up to two menstrual cycles. Results: Among ovulatory cycles with recorded cycle lengths (n = 463), there were 41 cycles (8.9%) with clinical LPD, 39 cycles (8.4%) with biochemical LPD, and 20 cycles (4.3%) meeting both criteria. Recurrent clinical and biochemical LPD was observed in eight (3.4%) and five (2.1%) women, respectively. Clinical and biochemical LPD were each associated with lower follicular estradiol (both P ≤ .001) and luteal estradiol (P = .03 and P = .02, respectively) after adjusting for age, race, and percentage body fat. Clinical, but not biochemical, LPD was associated with lower LH and FSH across all phases of the cycle (P ≤ .001). Conclusions: Clinical and biochemical LPD were evident among regularly menstruating women. Estradiol was lower in LPD cycles under either criterion, but LH and FSH were lower only in association with shortened luteal phase (ie, clinical LPD), indicating that clinical and biochemical LPD may reflect different underlying mechanisms. Identifying ovulation in combination with a well-timed luteal progesterone measurement may serve as a cost-effective and specific tool for LPD assessment by clinicians and researchers.
Full-text available
Progesterone is essential for endometrial receptivity and successful establishment of pregnancy. Either an insufficient progesterone concentration or an insufficient response to progesterone, therefore can lead to infertility and pregnancy loss. Assessment of the role that either progesterone insufficiency or inadequate progesterone response plays in human reproductive failure has been difficult to assess because serum progesterone concentrations fluctuate markedly, limiting the ability to characterize sufficiency of progesterone, and there are no highly reliable markers of endometrial function available. Recent evidence demonstrates exquisite sensitivity of normal endometrium to very low levels of progesterone stimulation, suggesting that progesterone insufficiency should not be a common cause of reproductive failure. Further evidence suggests that women with endometriosis, and possibly polycystic ovarian syndrome, have an altered progesterone response, which may explain some of the clinical features of these disorders and supports the hypothesis that progesterone resistance underlies some cases of human reproductive failure.
Progesterone production from the corpus luteum is critical for natural reproduction. Progesterone supplementation seems to be an important aspect of any assisted reproductive technology treatment. Luteal phase deficiency in natural cycles is a plausible cause of infertility and pregnancy loss, though there is no adequate diagnostic test. This article describes the normal luteal phase of the menstrual cycle, investigates the controversy surrounding luteal phase deficiency, and presents the current literature for progesterone supplementation during assisted reproductive technologies. Copyright © 2015 Elsevier Inc. All rights reserved.
Common endocrinopathies are a frequent contributor to spontaneous and recurrent miscarriage. Although the diagnostic criteria for luteal phase defect (LPD) is still controversial, treatment of patients with both recurrent pregnancy loss and LPD using progestogen in early pregnancy seems beneficial. For patients who are hypothyroid, thyroid hormone replacement therapy along with careful monitoring in the preconceptual and early pregnancy period is associated with improved outcome. Women with polycystic ovary syndrome (PCOS) have an increased risk of pregnancy loss. Management of PCOS with normalization of weight or metformin seems to reduce the risk of pregnancy loss.
Infertility is a common condition, affecting 15% of couples trying to conceive. The infertility evaluation includes an assessment of both the female and the male partner to discern the factors contributing to their difficulty in conceiving. The basic evaluation includes a careful history of both partners, physical examination of the female partner, investigation of ovulatory function and tubal status, and semen analysis. A more detailed investigation is performed as dictated by individual factors.
The term 'luteal phase deficiency' was first coined more than 60 years ago, and, since then, it has been suggested as a clinical entity per se and an aetiological factor for subfertility, implantation failure and recurrent miscarriage. Despite the existing recommendations for rational work-up in subfertility, luteal phase evaluation and progesterone therapy alone is still common in daily practice. This review comprises results from a Pubmed literature search with the terms 'luteal phase' and 'subfertility', focussing on clinical situations not primarily related to assisted reproduction techniques. Additional data from the experimental studies published in the past 10 years on follicular maturation, oocyte developmental competence and the ovulatory cascade are integrated into the clinical continuum of dysfunctional ovulation, menstrual cycle irregularity and impaired corpus luteum function. As reliable diagnostic tools for adequate luteal function are missing, the presence of clinical symptoms such as cycle irregularity or premenstrual spotting is indicative and should initiate early follicular phase diagnostic work-up. New evidence on the interdependence of oocyte and follicular maturation and resulting developmental competence of the embryo further support the use of ovarian stimulation as the first-line therapeutic option in different subsets of patients with subfertility including luteal phase deficiency.
This retrospective study investigated whether mid-luteal serum progesterone concentrations are associated with live birth rates in women with WHO group II anovulatory infertility undergoing ovulation induction. Data were from women (n = 335) stimulated with gonadotrophins using a low-dose step-up protocol, of which women with presumptive ovulation (n = 279), defined as a mid-luteal progesterone concentration ⩾7.9 ng/ml (⩾25 nmol/l; range 7.9-194 ng/ml) were included. Of the women with presumptive ovulation, 57 (20.4%) had a live birth and their serum mid-luteal progesterone concentration was significantly (P = 0.016) higher than that of the non-live birth group. There were significant associations between the number of large (⩾15 mm) and medium-sized follicles (12-14 mm) at human chorionic gonadotrophin administration and the mid-luteal progesterone concentration (P < 0.001), while the total number of large and medium-sized follicles was not significantly associated with live birth rate. In conclusion, mid-luteal progesterone concentrations above the cut-off values currently used for defining ovulation were positively associated with live birth rates in normogonadotrophic anovulatory women undergoing ovulation induction with gonadotrophins. The mid-luteal progesterone concentration, apart from being a consequence of the number of corpora lutea, may also reflect the quality of the follicle/oocyte/corpus luteum.
The luteinized unruptured follicle syndrome (LUF) is diagnosed in different numbers of cycles and its place in sterility etiology still has to be established. This article reviews today's diagnostic possibilities, the occurrence of LUF in patients with different types of sterility, the etiology and therapeutic approaches.
The nature and incidence of normal and abnormal spontaneous ovarian cycles, identified with ultrasound and endocrine tracking, were examined in 45 regularly cycling infertile women with no definitive cause and 15 women who were apparently normal and were receiving donor insemination because of clearly infertile partners. In 136 cycles, four apparently distinct abnormal patterns were detected. The total incidence in the infertile group was 58% compared with 23% in the donor insemination group (P less than 0.005). Twelve of 26 subjects who had at least three cycles tracked showed two different abnormalities, and 1 subject had three different abnormalities in five abnormal cycles. These results suggest that abnormal cycles are a significant factor in unexplained infertility and that diagnosis and treatment cannot be based on the study of a single cycle.