Luteal phase deficiency: pathophysiology and role in reproductive disorders

Medical Council ◽

10.21518/2079-701x-2021-3-89-97 ◽

2021 ◽

pp. 89-97

Author(s):

I. A. Ivanov

Keyword(s):

Corpus Luteum ◽

Luteal Phase ◽

Pregnancy Loss ◽

Embryo Implantation ◽

Endometrial Biopsy ◽

Reproductive Disorders ◽

Normal Functioning ◽

Art Programs ◽

Progesterone Secretion ◽

Lh Secretion

It is well known that corpus luteum normal functioning is crucial for the luteal phase, which determines the embryo implantation and the progression of pregnancy. Luteal phase deficiency (LPD), associated with impaired progesterone secretion by the corpus luteum, is considered as a significant factor of infertility and early pregnancy loss, both in the natural cycle and in assisted reproductive technology (ART) programs. The LPD formation is associated with hypothalamic-pituitary-ovarian axis dysregulation, which leads to abnormal secretion of FSH, LH, ovulation and luteinization disorders, premature luteolysis. The most significant problem in the study of LPD is the lack of reliable and reproducible methods of its verification. This review summarizes the available data on the methods and issues of LPD diagnosing, including the duration of the luteal phase, the level of progesterone secretion, and endometrial biopsy. LPD is an important factor in reproductive failures during IVF, which is caused by suppression of the physiological FSH, LH secretion and requires mandatory progesterone support in the luteal phase of the cycle. It’s hard to define the contribution of LPD to miscarriage, however, empirical progestogen therapy may increase the live births rate in women with recurrent pregnancy loss. Currently, there is no evidence of the LPD role and progesterone support effectiveness in infertility management, so the diagnosis and therapy of LPD among these patients should not be considered.

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Hubungan Kadar Progesteron pada Fase Awal Luteal dengan Kematian Embrio pada Sapi Aceh

Jurnal Agripet ◽

10.17969/agripet.v19i2.14881 ◽

2019 ◽

Vol 19 (2) ◽

pp. 107-112

Author(s):

Budianto Panjaitan ◽

Citra Chyntia Helwana ◽

Nellita Meutia ◽

Yusmadi Yusmadi ◽

Tongku Nizwan Siregar ◽

...

Keyword(s):

Body Weight ◽

Corpus Luteum ◽

Adult Female ◽

Artificial Insemination ◽

Luteal Phase ◽

Embryonic Mortality ◽

Progesterone Concentration ◽

Double Injection ◽

Progesterone Secretion ◽

Embryonic Death

ABSTRAK. Progesteron merupakan hormon yang berperan penting dalam proses pemeliharaan kebuntingan dan dihasilkan oleh corpus luteum. Penelitian ini bertujuan mengetahui hubungan antara kadar hormon progesteron pada fase awal luteal dengan kematian embrio pada sapi Aceh. Dalam penelitian ini digunakan empat ekor sapi betina dewasa berumur 3-5 tahun, bobot badan 150-250 kg, sehat secara klinis, dan memiliki reproduksi normal. Sapi disinkronisasi menggunakan 5 ml prostaglandin F2 alfa (PGF2α) dengan pola penyuntikan ganda berinterval 11 hari. Koleksi sampel darah untuk pengukuran konsentrasi progesteron dilakukan pada hari ke-5, 6, dan 7 pasca inseminasi. Pengukuran konsentrasi progesteron dilakukan menggunakan metode enzymelinked-immunoassay (ELISA), pemeriksaan kebuntingan dan kematian embrio menggunakan metode transrektal ultrasonografi pada hari ke-25 pasca inseminasi. Pemeriksaan diulang setiap 10 hari sampai hari ke-55 pasca inseminasi. Puncak sekresi progesteron pada sapi bunting dengan embrio yang bertahan hidup terdapat pada hari ke-7 (2,082 ng/ml), pada sapi Late Embryonic Mortality (LEM) di hari ke-5 (8,209 ng/ml) dan pada sapi tidak bunting di hari ke-7 (3,051±1,157 ng/ml). Sekresi progesteron sapi LEM pada hari ke-5 sampai dengan ke-7 cenderung menurun sedangkan pada sapi yang bertahan hidup cenderung meningkat. (Correlation between progesterone levels in early luteal phase and embryonic death in Aceh cattle) ABSTRACT. Progesterone is an important hormone that functions to maintain pregnancy and is produced by the corpus luteum. The aim of this study was to see a correlation between progesterone and the incidence of embryonic death in Aceh cattle. This study used four adult female cows, 3-5 years old, 150-250 kg body weight, clinically healthy, and have a normal reproduction. The synchronized with 5 ml prostaglandin F2 alfa hormone, and double injection pattern with 11-day intervals. The blood was collected for progesterone measurements on 5th, 6th, 7th day post artificial insemination. Measurement of progesterone concentration was carried out using an enzymelinked-immunoassay (ELISA), while pregnancy and embryo mortality was performed using the trans-rectal ultrasonography method on the 25th day after insemination. The examination was repeated every 10 days until day 55th after insemination. Progesterone secretion peaks in pregnant cows were on day 7th (2.082 ng/ml), in cattle Late Embryonic Mortality (LEM) on day 5th (8.209 ng/ml) and in cattle not pregnant on day 7th (3.051±1.157 ng/ml). The pattern of LEM progesterone secretion on days 5th to 7th tends to decrease while those that survive tend to increase.

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Delayed effect of low progesterone concentrations on bovine uterine PGF(2alpha) secretion in the subsequent oestrous cycle

Reproduction ◽

10.1530/rep.0.1220643 ◽

2001 ◽

pp. 643-648 ◽

Cited By ~ 32

Author(s):

A Shaham-Albalancy ◽

Y Folman ◽

M Kaim ◽

M Rosenberg ◽

D Wolfenson

Keyword(s):

Corpus Luteum ◽

Luteal Phase ◽

Oestrous Cycle ◽

Delayed Effect ◽

Plasma Progesterone ◽

Progesterone Secretion ◽

Progesterone Treatment ◽

Late Luteal Phase ◽

Subsequent Cycle ◽

Concentration Curves

Low progesterone concentrations during the bovine oestrous cycle induce enhanced responsiveness to oxytocin challenge late in the luteal phase of the same cycle. The delayed effect of low progesterone concentrations during one oestrous cycle on uterine PGF(2alpha) secretion after oxytocin challenge on day 15 or 16 of the subsequent cycle was studied by measuring the concentrations of the major PGF(2alpha) metabolite (13,14-dihydro-15-keto PGF(2alpha); PGFM) in plasma. Two experiments were conducted, differing in the type of progesterone treatment and in the shape of the low progesterone concentration curves. In Expt 1, progesterone supplementation with intravaginal progesterone inserts, with or without an active corpus luteum, was used to obtain high, or low and constant plasma progesterone concentrations, respectively. In Expt 2, untreated cows, representing high progesterone treatment, were compared with cows that had low but increasing plasma progesterone concentrations that were achieved by manipulating endogenous progesterone secretion of the corpus luteum. Neither experiment revealed any differences in plasma progesterone concentrations between the high and low progesterone groups in the subsequent oestrous cycle. In both experiments, both groups had similar basal concentrations of PGFM on day 15 (Expt 1) or 16 (Expt 2) of the subsequent oestrous cycle, 18 days after progesterone treatments had ended. In both experiments, the increases in PGFM concentrations in the low progesterone groups after an oxytocin challenge were markedly higher than in the high progesterone groups. These results indicate that low progesterone concentrations during an oestrous cycle have a delayed stimulatory effect on uterine responsiveness to oxytocin during the late luteal phase of the subsequent cycle. This resulting increase in PGF(2alpha) secretion may interfere with luteal maintenance during the early stages of pregnancy.

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Evidence for luteotrophic and antiluteolytic actions of prolactin in rats with 5-day oestrous cycles

Journal of Endocrinology ◽

10.1677/joe.0.1170455 ◽

1988 ◽

Vol 117 (3) ◽

pp. 455-460 ◽

Cited By ~ 6

Author(s):

J. E. Sánchez-Criado ◽

P. van der Schoot ◽

J. Th. J. Uilenbroek

Keyword(s):

Biological Activity ◽

Corpus Luteum ◽

Reproductive Cycle ◽

Prolactin Secretion ◽

Ovarian Cycle ◽

Progesterone Secretion ◽

Lh Secretion

ABSTRACT Injection of 1 mg bromocriptine at either 08.00 or 16.00 h on the day of oestrus in rats with 5-day oestrous cycles caused a reduction in the duration of progesterone secretion by the corpus luteum during dioestrous, and a shortening of the ovarian cycle by 1 day. These effects were not present when bromocriptine was injected at 08.00 h on the day of metoestrus. The effect of bromocriptine on progesterone secretion by the corpus luteum was reversed by neutralization of the biological activity of LH at dioestrus by injection of 0·5 ml anti-LH serum at 08.00 h at metoestrus. Injection of the antiserum alone prolonged progesterone secretion by the corpus luteum, but had no effect on the length of dioestrus. These results are interpreted as suggesting (1) that prolactin secretion on the afternoon of oestrus protects the corpus luteum of the rat ovarian cycle against the luteolytic effects of LH secretion during early dioestrus and (2) that prolactin stimulates progesterone secretion in the absence of such a luteolytic action. This response of the corpus luteum of the rat ovarian reproductive cycle to prolactin results in 5-day oestrous cycles. J. Endocr. (1988) 117, 455–460

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A Prospective, Randomized Study of Endometrial Telomerase during the Menstrual Cycle

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.8.7729 ◽

2001 ◽

Vol 86 (8) ◽

pp. 3912-3917 ◽

Cited By ~ 18

Author(s):

Christopher D. Williams ◽

John F. Boggess ◽

L. Robert LaMarque ◽

William R. Meyer ◽

Michael J. Murray ◽

...

Keyword(s):

Menstrual Cycle ◽

Luteal Phase ◽

Randomized Study ◽

Embryo Implantation ◽

Telomerase Activity ◽

Endometrial Biopsy ◽

Uterine Receptivity ◽

Serum Progesterone ◽

Proliferative Phase ◽

Late Luteal Phase

The purpose of this study was to characterize telomerase activity during the menstrual cycle, focusing on the luteal phase. A total of 84 endometrial biopsy samples were obtained from 72 participants. Daily urinary LH testing (OvuQuick, Quidel) was used to establish the day of the LH rise, and participants were randomized to return during the secretory phase. Twelve women returned on the identical day during the luteal phase of a subsequent cycle to allow intercycle comparisons of telomerase activity. Telomerase activity was evaluated using a modified TRAP-eze (Intergen) detection protocol. At the time of each endometrial biopsy, serum estrogen and progesterone were measured. Proliferative phase endometrium showed high telomerase activity. At the onset of the luteal phase telomerase activity was high, but it decreased during the early luteal phase, disappeared by the midluteal phase (6 d after LH surge detected), and then rose to moderate levels in the late luteal phase beginning on luteal d 10. Serum progesterone levels were inversely related to telomerase activity. In conclusion, endometrial telomerase activity is dynamic: high during the proliferative phase but inhibited during the midsecretory phase of the menstrual cycle. The timing of expression coincides with the rise and fall of progesterone levels and the time period of maximal uterine receptivity for embryo implantation. This supports a relationship between sex steroid levels and telomerase regulation.

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The Endometrial Immune Profiling May Positively Affect the Management of Recurrent Pregnancy Loss

Frontiers in Immunology ◽

10.3389/fimmu.2021.656701 ◽

2021 ◽

Vol 12 ◽

Author(s):

Meryam Cheloufi ◽

Alaa Kazhalawi ◽

Anne Pinton ◽

Mona Rahmati ◽

Lucie Chevrier ◽

...

Keyword(s):

Live Birth ◽

Pregnancy Loss ◽

Embryo Implantation ◽

Live Birth Rate ◽

Endometrial Biopsy ◽

Three Dimension ◽

Uterine Receptivity ◽

Hormonal Stimulation ◽

Personalized Care ◽

Immune Profiling

IntroductionThe endometrial immune profiling is an innovative approach based on the analysis of the local immune reaction occurring in the endometrium at the time of the embryo implantation. By documenting the local immune activation during the period of uterine receptivity, we aim to detect and correct potential imbalances before and at the very beginning of placentation. The main objective of the study was to analyze in women with a history of repeated pregnancy loss (RPL) the association of personalized strategies based on immune dysregulations with live birth rates. The secondary objective was to highlight the main prognostic factors for live births.MethodsThis is an observational retrospective analysis of 104 patients with RPL, included between January 2012 and December 2019. Inclusion criteria included a spontaneous fertility with at least three miscarriages, an assessment including a three-dimension ultrasound scan, an endometrial biopsy for uterine immune profiling and a follow-up over at least 6 months with personalized care if indicated after the complete assessment. We defined as a success if the patients had a live birth after the suggested plan, as a failure if the patient either did not get pregnant or experienced a new miscarriage after the targeted therapies.ResultsUterine immune profiling was the only exploration to be significantly associated with a higher live birth rate (LBR) if a dysregulation was identified and treated accordingly (55% vs 45%, p=0.01). On the contrary, an absence of local dysregulation (resulting in an apparently balanced immune environment) was associated with a higher risk of a new miscarriage, suggesting that the cause inducing RPL still needed to be identified. Independently of age and AMH level, dysregulated immune profile is significatively associated with 3 times higher LBR than a non-deregulated profile (OR=3.4 CI 95%1.27-9.84) or five times in case of an overactive profile treated by immunotherapy (OR=5 CI 95% 1.65-16.5). The usage of ART was significantly associated with lower LBR regardless of the presence of a subfertility factor (p=0.012). Personalization of medical care using natural cycle or simple hormonal stimulation is associated with a significantly higher LBR than personalization including ART treatments regardless of maternal age and AMH level (OR= 2.9 CI 95% 1.03-8.88).ConclusionOur study suggests that some endometrial immune profiles with targeted management of RPL are associated with a higher rate of LBR. ART may be negatively associated with LBR.

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ASPECTS OF THE REGULATION OF CORPUS LUTEUM FUNCTION IN ANDROGEN-STERILIZED FEMALE RATS

Acta Endocrinologica ◽

10.1530/acta.0.0460571 ◽

1964 ◽

Vol 46 (4) ◽

pp. 571-579 ◽

Cited By ~ 9

Author(s):

G. H. Zeilmaker

Keyword(s):

Pituitary Gland ◽

Corpus Luteum ◽

Luteal Phase ◽

Female Rats ◽

Male Rats ◽

Corpora Lutea ◽

Normal Female ◽

Cervical Stimulation ◽

Lh Secretion

ABSTRACT Some aspects of the regulation of function of artificially induced corpora lutea in androgen-sterilized female rats have been studied. The morphology of the vaginal epithelium and the distribution of sudanophilic materials in the luteal cells served as criteria for possible corpus luteum function. Pseudopregnancy, i. e. corpus luteum function during a defined period, as can be observed in female rats after sterile copulation, could not be induced in androgen-sterilized rats by daily cervical stimulation, by three daily injections of reserpine or by the presence of an isotransplanted pituitary gland during the first four days after the induction of corpus luteum formation. Prolonged corpus luteum function during at least 45 days was observed in animals bearing an isotransplanted pituitary gland under the kidney capsule. It is suggested that the evenly distributed sudanophilia in these corpora lutea is a result of the »tonic LH secretion« of the pituitary gland in situ. Comparison with similar studies in male rats led to the conclusion that an ovulation-inducing release of gonadotrophins plays a major role in the termination of the luteal phase in normal female rats. In ovariectomized androgen-sterilized rats treated with progesterone and oestrone a decreased response of the uterus to a traumatic stimulus was noticed as compared with the response in similarly treated normal rats.

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SUPPRESSION OF LUTEAL PROGESTERONE SECRETION IN THE STUMPTAILED MACAQUE BY AN ANTAGONIST ANALOGUE OF LUTEINIZING HORMONE RELEASING HORMONE.

Journal of Endocrinology ◽

10.1677/joe.0.104r001 ◽

1985 ◽

Vol 104 (2) ◽

pp. R1-R4 ◽

Cited By ~ 19

Author(s):

H.M. Fraser ◽

D.T. Baird ◽

G.I. McRae ◽

J.J. Nestor ◽

B.H. Vickery

Keyword(s):

Corpus Luteum ◽

Luteal Phase ◽

Releasing Hormone ◽

Expected Time ◽

Progesterone Secretion ◽

Serum Lh ◽

Late Luteal Phase ◽

Serum Hormone ◽

Lhrh Antagonist ◽

Lh Releasing Hormone

ABSTRACT The dependence of progesterone secretion from the corpus luteum on pituitary gonadotrophin was examined in the cyclic stumptailed macaque by studying the effects of a single s.c. injection of a potent LH releasing hormone (LHRH) antagonist, [N–Ac–D–Nal(2)1, D–pCl–phe2, D–Trp3, D–hArg(Et2)6, D–Ala10] LHRH. A dose of 100 μg antagonist/kg administered on days 9/10 of the luteal phase in three monkeys caused a marked temporary suppression of serum concentrations of LH and progesterone during the following 32 h but levels still remained detectable and after 2 days serum hormone concentrations returned to the normal luteal-phase range. When the same animals were treated with 300 μg antagonist/kg at the same period during a subsequent cycle, serum LH levels were close to or at the limits of detection of the bioassay for the next 48 h and progesterone concentrations declined steadily, reaching non-detectable values by 48 h. In two monkeys the progesterone levels remained suppressed and they menstruated prematurely; in the third monkey the progesterone concentration rose to just above baseline and menstruation occurred at the expected time. Administration of 300μg antagonist/ kg on days 6/7 of the luteal phase in a further three monkeys also suppressed progesterone concentrations but not to baseline values, and after 2 days a normal progesterone profile was regained. These results suggest that the corpus luteum of the stumptailed macaque is largely dependent on pituitary gonadotrophin support during the mid to late luteal phase.

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PROGESTERONE IN THE HUMAN PERIPHERAL BLOOD IN THE PREOVULATORY PERIOD OF THE MENSTRUAL CYCLE

Acta Endocrinologica ◽

10.1530/acta.0.0550091 ◽

1967 ◽

Vol 55 (1) ◽

pp. 91-96 ◽

Cited By ~ 9

Author(s):

Benno Runnebaum ◽

Josef Zander

Keyword(s):

Menstrual Cycle ◽

Corpus Luteum ◽

Peripheral Blood ◽

Human Peripheral Blood ◽

Progesterone Concentration ◽

Plasma Progesterone ◽

Progesterone Secretion ◽

Graafian Follicle ◽

The Mean ◽

Mean Concentration

ABSTRACT Progesterone was determined and identified in human peripheral blood during the preovulatory period of the menstrual cycle, by combined isotope derivative and recrystallization analysis. The mean concentration of progesterone in 1.095 ml of plasma obtained 9 days before ovulation was 0.084 μg/100 ml. However, the mean concentration of progesterone in 1.122 ml of plasma obtained 4 days before ovulation was 0.279 μg/100 ml. These data demonstrate a source of progesterone secretion other than the corpus luteum. The higher plasma-progesterone concentration 4 days before ovulation may indicate progesterone secretion of the ripening Graafian follicle of the ovary.

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