Tải bản đầy đủ - 0 (trang)
3 Treatment of Folliculo-Luteal Insufficiency with  Low-­Dosage Corticoid or Combined Corticoid and Clomiphene Citrate Therapy

3 Treatment of Folliculo-Luteal Insufficiency with  Low-­Dosage Corticoid or Combined Corticoid and Clomiphene Citrate Therapy

Tải bản đầy đủ - 0trang




While other researchers complement CC treatment with DEX treatment applied

in a defined part of the cycle (2 mg/day dose between the 5th and 15th cycle day,

Moradan and Gharbani 2009) to treat unexplained infertility, we used continuously

administered DEX treatment of 0.5 mg dose every evening. In case of conception,

we stopped treatment when we obtained a positive pregnancy test result. We chose

continuous treatment as the decrease of GnRH secretion exerts a negative effect in

each phase of the cycle. Inhibiting FSH levels at the beginning of the cycle disturbs

the emergence of a physiological cycle similarly to the negative effects on the LH

peak or on the essential LH secretion during the luteal phase. If the treatment is

applied in the evening, a lower dosage is sufficient to achieve the desired effect due

to the early morning maximum cortisol secretion. Moreover, daily treatment with

0.5 mg of DEX involves no risks, and the development of any considerable adverse

side effects is unlikely during its application (ASRM 2006).

Continuous, low-dose DEX treatment alone was primarily used in patients who

exhibited HAN (hirsutism with elevated free testosterone levels) besides FLI and, in

cases with cycles that were unstable, varying in length or oligomenorrhoeal. FLF

normalised in 45 % of patients with DEX treatment alone (average p > 23 ng/ml). In

51 % of patients, FLF normalised by adding 5 × 50 mg CC and in 4 % of patients by

adding 5 × 100 mg CC (Fig. 4.2).

We used combined CC + DEX treatment (first CC alone and then CC + DEX)

primarily in patients who responded poorly to CC treatment compared to the average. In all three groups in which we complemented 5 × 100 mg (35 %), 5 × 150 mg

(47 %) and 5 × 200 mg (18 %) CC treatment with DEX, a very positive effect was

observed, with P values over 30 ng/ml (Fig. 4.3). On this basis, in case of insufficient CC efficacy, it seems reasonable to complement the treatment with DEX even

at a dose of 5 × 100 mg CC if this causes a moderate P increase.

We found an especially beneficial effect of DEX complementation in patients

whose measured P values varied under identical CC dosage. It is presumably the

varying intensity of stress that underlies the different treatment responses of such

cases, the effect of which is favourably diminished by DEX treatment.



As the causal role of enhanced adrenal cortex function in the development of associated reproductive function disorders is already accepted in HAN cases (hirsutism,

increased androgen secretion), corticoid suppression of the HPA axis has been used

to treat these conditions for decades (Greenblatt 1953; Jones et al. 1953). The normalisation of cycle disturbances was observed in 60–100 % of the cases as an effect

of DEX or prednisone treatment (Abraham 1981; Yuen and Mincey 1983; Birnbaum

and Rose 1984), and conception took place in 66 % of the cases (Casey et al. 1966).

Sarries et al. (1978) achieved 55 pregnancies – only 5 (9 %) out of which ended in

abortion – with continuous prednisone treatment in 30 patients with an anamnesis

of 20 (91 %) abortions out of 22 pregnancies, which supports the causal role of

adrenal HAN in associated FLI and the occurrence of abortion it causes.



Treatment of Folliculo-Luteal Insufficiency





















12 ,0







5x200mg CC

5x150mg CC

5x100mg CC

basal value

* DEX +



500 CC

750 CC

1000 CC




* doses required to achieve phisiological luteal function

Fig. 4.3 The required dose of combined clomiphene citrate (CC) and dexamethasone (DEX)

treatment to achieve physiological FLF * (N = 85)

Many authors achieved positive results by CC treatment complemented with

DEX or prednisolone in the case of anovulation or PCOS (Lobo et al. 1982; Daly

et al. 1984; Trott et al. 1996; Isaacs et al. 1997; Elnashar et al. 2006). In literature

reviews (Cochrane database), completing CC treatment with DEX seemed remarkably favourable against CC treatment alone (OR 9.46) in PCOS and in anovulatory

conditions without PCOS as well (Beck et al. 2005; Brown et al. 2009). Combined

CC + DEX treatment of unexplained infertility is only reported in the publication of

Moradan and Ghorbani (2009). Better monthly pregnancy rates were achieved by

CC + DEX treatment than by CC treatment alone (21.4 % and 4.5 %, respectively).


Abraham GE. Adrenal androgens in hirsutism. In: Genazzani AR, Thijssen JHH, Siiteri PK, editors. Adrenal androgens. New York: Raven; 1981. p. 267–82.

Agarwal SK, Buyalos RP. Corpus luteum function and pregnancy rates with clomiphene citrate

therapy: comparison of human chorionic gonadotrophin-induced versus spontaneous ovulation.

Hum Reprod. 1995;10:328–31.



Al-Inany H, Azab H, El-Khayat W, Nada A, El-Khattan E, Abou-Setta AM. The effectiveness of

clomiphene citrate in LH surge suppression in women undergoing IUI: a randomized controlled

trial. Fertil Steril. 2010;94(6):2167–71.

ASRM. Use of clomiphene citrate in women. Fertil Steril. 2006;86:S187–93.

ASRM. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril.


ASRM. The clinical relevance of luteal phase deficiency: a committee opinion. Fertil Steril.


ASRM. Use of clomiphene citrate in infertile women: a committee opinion. Fertil Steril.


ASRM-ESHRE, Luca G, Catherine R, Joep G, Marcelle C, Antonis M, Lobo RA. Best practices of

ASRM and ESHRE: a journey through reproductive medicine. Fertil Steril.


Badawy A, Elnashar A, Totongy M. Clomiphene citrate or aromatase inhibitors for superovulation

in women with unexplained infertility undergoing intrauterine insemination: a prospective

randomized trial. Fertil Steril. 2009a;92(4):1355–9.

Badawy A, Shokeir T, Allam AF, Abdelhady H. Pregnancy outcome after ovulation induction with

aromatase inhibitors or clomiphene citrate in unexplained infertility. Acta Obstet Gynecol

Scand. 2009b;88:187–91.

Beck JI, Boothroyd C, Proctor M, Farquhar C, Hughes E. Oral anti-oestrogens and medical

adjuncts for subfertility associated with anovulation. Cochrane Database Syst Rev.


Birnbaum MD, Rose LI. Late onset adrenocortical hydroxylase deficiencies associated with menstrual dysfunction. Obstet Gynecol. 1984;63:445–9.

Branch DW, Gibson M, Silver RM. Recurrent miscarriage. N Engl J Med. 2010;363:1740–7.

Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E. Clomiphene and anti-oestrogens for ovulation induction in PCOS. Cochrane Database Syst Rev. 2009;(4):CD002249

Casey JH, Hj B, Kent JR, Kellie GE, Moxham A, Nabarro J, Nabarro JDN. Treatment of hirsutism

by adrenal and ovarian suppression. J Clin Endocrinol Metab. 1966;26:1370–5.

Check JH, Adelson HG. The efficacy of progesterone in achieving successful pregnancy. II. In

women with pure luteal phase defects. Int J Fertil. 1987;32:139–41.

Check JH, Wu CH, Adelson HG. Bromocriptine versus progesterone therapy for infertility related

to luteal phase defects in hyperprolactinemic patients. Int J Fertil. 1989;34:209–14.

Cook CL, Schroeder JA, Yussman MA, Sanfilippo JS. Induction of luteal phase defect with clomiphene citrate. Am J Obstet Gynecol. 1984;149:613–6.

Csapó ÁI, Pulkkinen M. Indispensability of the human corpus luteum in the maintenance of early

pregnancy: lutectomy evidence. Obstet Gynecol Surv. 1978;3:69–81.

Dallenbach-Hellweg G. The endometrium of infertility. A review. Pathol Res Pract.


Daly DC, Walters CA, Soto Albors CE, Riddick DH. Endometrial biopsy during treatment of luteal

phase defects is predictive of therapeutic outcome. Fertil Steril. 1983;40:305–10.

Daly DC, Walters CA, Soto-Albors CE, Tohan N, Riddick DH. A randomized study of dexamethasone in ovulation induction with clomiphene citrate. Fertil Steril. 1984;41:844–8.

Daya S. Efficacy of progesterone support for pregnancy in women with recurrent miscarriage. A

meta-analysis of controlled trials. Br J Obstet Gynaecol. 1989;96(3):275–80.

Deaton JL, Clark RR, Pittaway DE, Herbst P, Bauguess P. Clomiphene citrate ovulation induction

in combination with a timed intrauterine insemination: the value of urinary luteinizing hormone

versus human chorionic gonadotropin timing. Fertil Steril. 1997;68(1):43–7.

Demoura MD, Ferriani RA, Desa MFS. Effects of clomiphene citrate on pituitary luteinizing hormone and follicle-stimulating hormone release in women before and after treatment with ethinyl estradiol. Fertil Steril. 1992;58:504–7.

Dickey RP, Olar TT, Curole DN, Taylor SN, Rye PH. Endometrial pattern and thickness associated

with pregnancy outcome after assisted reproduction technologies. Hum Reprod.




Treatment of Folliculo-Luteal Insufficiency

Dickey RP, Olar TT, Taylor SN, Curole DN, Rye PH. Sequential clomiphene citrate and human

menopausal gonadotrophin for ovulation induction: comparison to clomiphene citrate alone

and human menopausal gonadotrophin alone. Hum Reprod. 1993;8(1):56–9.

Dickey RP, Holtkamp DE. Development, pharmacology and clinical experience with clomiphene

citrate. Hum Reprod Update. 1996;62:483–506.

Dickey RP, Hower JF. Relationship of estradiol and progesterone levels to uterine blood flow

during early pregnancy. Early Pregnancy. 1996;2:113–20.

Dickey RP, Taylor SN, Rye PH, Lu PY. Future use of clomiphene in ovarian stimulation. A role for

clomiphene in the 21st century? Hum Reprod. 1998;13(9):2361–2.

Dickey RP, Taylor SN, Lu PY, Sartor BM, Rye PH, Pyrzak R. Effect of diagnosis, age, sperm quality, and number of preovulatory follicles on the outcome of multiple cycles of clomiphene

citrate-intrauterine insemination. Fertil Steril. 2002;78:1088–95.

Elnashar A, Abdelmageed E, Fayed M, Sharaf M. Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebocontrolled study. Hum Reprod. 2006;21:1805–8.

ESHRE. Guidelines to the prevalence, diagnosis, treatment and management of infertility. Hum

Reprod. 1996;1996(11):1775–807.

Forman R, Fries N, Testart J, Belaisch Allart J, Hazout A, Frydman R. Evidence for an adverse

effect of elevated serum estradiol concentrations on embryo implantation. Fertil Steril.


Fossum GT, Vermesh M, Kletzky OA. Biochemical and biophysical indices of follicular development in spontaneous and stimulated ovulatory cycles. Obstet Gynecol. 1990;75:407–11.

Fredericsson B, Carlstrom K, Björk G, Messinis I. Effect of prolactin and bromocriptine on the

luteal phase in infertile women. Eur J Obstet Gynecol Reprod Biol. 1981;11:319–33.

Fritz MA, Holmes RT, Keenan EJ. Effect of clomiphene citrate treatment on endometrial estrogen

and progesterone receptor induction in women. Am J Obstet Gynecol. 1991;165:177–85.

Glazener CM, Bailey J, Hull MG. Effectiveness of vaginal administration of progesterone. Br

J Obstet Gynaecol. 1985;92:364–8.

Greenblatt RB. Cortisone in treatment of the hirsute women. Am J Obstet Gynecol.


Guzick DS, Zeleznik A. Efficacy of clomiphene citrate in the treatment of luteal phase deficiency:

quantity versus quality of preovulatory follicles. Fertil Steril. 1990;54:206–10.

Hammond MG, Talbert LM. Clomiphene citrate therapy of infertile women with low luteal phase

progesterone levels. Obstet Gynecol. 1982;59:275–9.

Hammond MG. Monitoring techniques for improved pregnancy rates during clomiphene ovulation

induction. Fertil Steril. 1984;42:499–509.

Hargrove JT, Maxson WS, Wentz AC. Absorption of oral progesterone is influenced by vehicle and

particle size. Am J Obstet Gynecol. 1988;161:948–51.

Hatasaka H. New perspectives for unexplained infertility. Clin Obst Gynecol. 2011;54:727–33.

Hill MJ, Whitcomb BW, Lewis TD, Wu M, Terry N, DeCherney AH, Levens ED, Propst

AM. Progesterone luteal support after ovulation induction and intrauterine insemination: a

systematic review and meta-analysis. Fertil Steril. 2013;100(5):1373–80.

Huang KE. The primary treatment of luteal phase inadequacy: progesterone versus clomiphene

citrate. Am J Obstet Gynecol. 1986;155:824–8.

Hughes E, Brown J, Collins JJ, Vanderkerchove P. Clomiphene citrate for unexplained subfertility

in women. Cochrane Database Syst Rev. 2010;(1):CD000057.

Isaacs Jr JD, Lincoln SR, Cowan BD. Extended clomiphene citrate (CC) and prednisone for the

treatment of chronic anovulation resistant to CC alone. Fertil Steril. 1997;67:641–3.

Jones GS. Some newer aspects of the management of infertility. JAMA. 1949;141:1123–8.

Jones GS, Howard JE, Lanford H. The use of cortisone in follicular phase disturbances. Fertil

Steril. 1953;4:492–6.

Jones GS, Pourmand K. An evaluation of etiologic factors and therapy in 555 private patients with

primary infertility. Fertil Steril. 1962;13:398–403.



Jones GS, Aksel S, Wentz AC. Serum progesterone values in the luteal phase defects: effect of

chorionic gonadotropin. Obstet Gynecol. 1974;44:26–34.

Jones GS. Corpus luteum: composition and function. Fertil Steril. 1990;54:21–6.

Li TC, Cooke ID. Evaluation of the luteal phase. Hum Reprod. 1991;6:484–99.

Lobo RA, Paul W, March CM, Granger L, Kletzky OA. Clomiphene and dexamethasone in women

unresponsive to clomiphene alone. Obstet Gynecol. 1982;60:497–501.

Martikainen H, Ronnberg L, Ruokonen A, Kauppila A. Effect of clomiphene citrate on prolactin

and gonadotropin release during GnRH-analog treatment. Gynecol Endocrinol. 1988;2:53–8.

Merviel P, Heraud MH, Grenier N, Lourdel E, Sanguinet P, Copin H. Predictive factors for pregnancy after intrauterine insemination (IUI): an analysis of 1038 cycles and a review of the literature. Fertil Steril. 2010;93:79–88.

Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with

an inadequate response to clomiphene citrate. Fertil Steril. 2001;75:305–9.

Mitwally MFM, Casper RF, Diamond MP. The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment. Reprod Biol Endocrinol.

2005;3:54–99 .

Moradan S, Ghorbani R. Dexamethasone in unexplained infertility. Saudi Med J. 2009;30:


Murray DL, Reich L, Adashi EY. Oral clomiphene citrate and vaginal progesterone suppositories

in the treatment of luteal phase dysfunction: a comparative study. Fertil Steril.


Nahoul K, Dehennin L, Jondet M, Roger M. Profiles of plasma estrogens, progesterone and their

metabolites after oral or vaginal administration of estradiol or progesterone. Maturitas.


Nakano R. Serum gonadotrophin and sex steroid hormone levels during mid-follicular and midluteal phases in hyperprolactinemic women with regular menstrual cycles. Br J Obstet

Gynaecol. 1987;94:142–6.

Norman TR, Morse CA, Dennerstein L. Comparative bioavailability of orally and vaginally

administered progesterone. Fertil Steril. 1991;56:1034–9.

Pavone ME, Bulun SE. Clinical review: The use of aromatase inhibitors for ovulation induction

and superovulation. J Clin Endocrinol Metab. 2013;98(5):1838–44.

Pearce JM, Hamid RI. Randomised controlled trial of the use of human chorionic gonadotrophin

in recurrent miscarriage associated with polycystic ovaries. Br J Obstet Gynaecol.


Polyzos NP, Tzioras S, Badawy AM, Valachis A, Dritsas C, Mauri D. Aromatase inhibitors for

female infertility:a systematic review of the literature. Reprod Biomed Online.


Pritts EA. Letrozole for ovulation induction and controlled ovarian hyperstimulation. Curr Opin

Obstet Gynecol. 2010;22(4):289–94.

Radwanska E, Hammond J, Smith P. Single midluteal progesterone assay in the management of

ovulatory infertility. J Reprod Med. 1981;26:85–9.

Radwanska E, Smith P, Hammond J. Correlation between preovulatory serum estradiol and midluteal progesterone levels during induction of ovulation with Clomid and HCG. J Reprod Med.


Randall JM, Templeton AA. The effects of clomiphene citrate upon ovulation and endocrinology

when administered to patients with unexplained infertility. Hum Reprod. 1991;6:659–64.

Ray A, Shah A, Gudi A, Homburg R. Unexplained infertility: an update and review of practice.

Repr Biomed Online. 2012;24:591–602.

Reindollar RH, Regan MM, Neumann PJ, Levine BS, Thornton KL, Alper MM, Goldman MB. A

randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track

and standard treatment (FASTT) trial. Fertil Steril. 2010;94(3):888–99.

Sagnella F, Moro F, Lanzone A, Tropea A, Martinez D, Capalbo A, Gangale MF, Spadoni V,

Morciano A, Apa R. A prospective randomized noninferiority study comparing recombinant



Treatment of Folliculo-Luteal Insufficiency

FSH and highly purified menotropin in intrauterine insemination cycles in couples with unexplained infertility and/or mild-moderate male factor. Fertil Steril. 2011;95(2):689–94.

Sarris S, Swyer GI, Ward RHT, Lawrence DM, McGarrigle NH, Little V. Treatment of mild adrenal hyperplasia and associated infertility with prednisone. Br J Obstet Gynaecol.


Simon JA, Gianfortoni JG, Hodgen GD. Clomiphene citrate attenuates hyperprolactinemia associated with ovarian hyperstimulation in the primate menstrual cycle. J Clin Endocrinol Metab.


Simon JA, Rocci ML, Robinson DE, Blake RE, Andrews MC, Hodgen GD, Hildebrand JR. The

absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone. Fertil Steril. 1993;60:26–33.

Soules MR, Bremner WJ, Steiner RA, Clifton DK. Prolactin secretion and corpus luteum function

in women with luteal phase deficiency. J Clin Endocrinol Metab. 1991;72:986–92.

Stouffer RL. Corpus luteum function and dysfunction. Clin Obstet Gynecol. 1990;33:668–89.

Szekeres-Bartho J, Balasch J. Progestagen therapy for recurrent miscarriage. Hum Reprod Update.


Trott EA, Plouffe Jr L, Hansen K, Hines R, Brann DW, Mahesh VB. Ovulation induction in clomiphene-resistant anovulatory women with normal dehydroepiandrosterone sulfate levels: beneficial effects of the addition of dexamethasone during the follicular phase. Fertil Steril.


Vanrell JA, Balasch J. Prolactin in the evaluation of luteal phase in infertility. Fertil Steril.


Vlahos NF, Coker L, Lawler C, Zhao Y, Bankowski B, Wallach EE. Women with ovulatory dysfunction undergoing ovarian stimulation with clomiphene citrate for intrauterine insemination

may benefit from administration of human chorionic gonadotropin. Fertil Steril.


Wenner R. Les antiprolactines. Actual Gynecol (Paris). 1975;6:91–5.

Wu CH, Winkel CA. The effect of therapy initiation day on clomiphene citrate therapy. Fertil

Steril. 1989;52(4):564–8.

Zreik TG, García-Velasco JA, Habboosh MS, Olive DL, Arici A. Prospective, randomized, crossover study to evaluate the benefit of human chorionic gonadotropin-timed versus urinary

luteinizing hormone-timed intrauterine inseminations in clomiphene citrate-stimulated treatment cycles. Fertil Steril. 1999;71:1070–4.


Recurrent Miscarriage and

Folliculo-Luteal Function

The term “recurrent miscarriage” means the abortion of two or more consecutive

pregnancies before the 24th week (the foetus is <500 g and/or <30 cm, ASRM 2008,

2013). In the past (but in many cases, even today), the diagnosis was made after

three or more spontaneous abortions (Berry et al. ETEP 1995; ESHRE/ASRM

2006). The abortion of two or more consecutive pregnancies occurs in 5 % of women

and of three or more in 1–3 %. In Hungary, two abortions are considered the criteria

for recurrent miscarriage from the beginning (Zoltán 1975; Papp 1999). Using these

criteria can be supported by the fact that adequate treatment applied after two abortions (see later) can prevent abortion, preterm birth and IUGR in 90–98 % of women

during the third pregnancy compared with those conceived without intervention.

Very few disorders of such importance have provoked the publication of so many

contradictions, inaccuracies and unfounded assumptions as recurrent miscarriage

(Stirrat 1990). Many authors have researched the role of genetic, immunologic, anatomical, endocrinological and other factors in the development of recurrent miscarriage (RM); nevertheless, no common view has yet emerged regarding their actual

causal role. We do not know any reason that would cause abortion in every subsequent pregnancy. This uncertainty is well indicated by the fact that almost 10,000

papers concerning RM have been published in recent decades, and the rates of successful childbearing have refused to change despite various therapeutic attempts.

From the patients of the University Clinic of Copenhagen who receive treatment for

recurrent miscarriage, 66 % give birth within 5 years and only 71 % within 15 years

(Lund et al. 2012). These results do not actually differ from the results of untreated

patients. In our patient material, 56 % of patients with a history of 3–9 abortions

give birth after the next pregnancy without treatment, and if we factor in the repeated

pregnancies of a proportion of patients, this ratio is approximately 70 %. The diagnostics of RM thus means discovering the risk factors that – if eliminated – we hope

will allow for a better prognosis (whereas not even a presumed risk factor can be

demonstrated in almost half of the patients and the abortion rates in this group are

similar to those of with almost any risk factor).

© Springer International Publishing Switzerland 2016

G. Siklósi, Role of Folliculo-luteal Function in Human Reproduction,

DOI 10.1007/978-3-319-39540-1_5




Recurrent Miscarriage and Folliculo-Luteal Function

Two certain connections are known regarding the outcome of subsequent pregnancy. First, the recurrence rate of spontaneous abortions increases in proportion to

the number of abortions in the medical history of the patient in question, and second,

abortions occur more frequently in parallel with maternal age (especially in patients

older than 35). Additionally, the extraordinary importance of RM in obstetrics arises

from the fact that the occurrence of preterm birth, intrauterine growth retardation

(IUGR) and foetal malformations, etc. increases by two to four times in parallel with

the number of abortions (Reginald et al. 1987). The most common causes of abortions – independent from the presence or absence of risk factors – are currently randomly occurring chromosomal abnormalities, usually numerical disorders that can

be detected in approximately 50 % of aborted pregnancies (Christiansen et al. 2005;

Branch et al. 2010; Tang and Quenby 2010; Sugiura-Ogasawara et al. 2014).


Most Investigated Causes and Risk Factors of Recurrent



Genetic Factors

Currently the most common (approximately 50 %) causes of recurrent miscarriage

(RM) are randomly occurring chromosomal abnormalities (CA), usually of numerical nature (90 %) (primarily trisomy, polyploidy, monosomy) that emerge during the

first two meiotic and the subsequent first three mitotic cell divisions of the oocyte.

The occurrence of CAs is thought to be more frequent in sporadic abortions (60–

70 %) by most authors, although van der Berg et al. (2012) found a 45 % occurrence

when summarising the data of 13 studies involving 7012 abortion cases. As maternal age increases, the occurrence of CAs increases rapidly, reaching up to 78 %

(Marquard et al. 2010). The ratio of these chromosomal abnormalities falls to

20–33 % in abortions between the 13th and 24th week (Rai and Regan 2006; Branch

et al. 2010; Tang and Quenby 2010; van der Berg et al. 2012). In a large patient

population, Ogasawara et al. (2000) showed that the number of abortions with normal karyotype rises relative to the number of abortions in the anamnesis; thus the

occurrence of numerical CAs is almost constant, independent of the number of

abortions (approximately 20 % calculated for all pregnancies). At the same time,

this means that with treatments initialised after conception, a maximum live-birth

rate of 80 % can be achieved in RM.

Structural chromosomal abnormalities are present in about 2 % of couples with

recurrent miscarriage, compared to 0.2 % in the average population. They occur in

less than 1 % in uncompensated form during the second trimester and in case of live

birth at a similar rate as in cases without abnormalities. Barber et al. (2010) detected

compensated translocation in 406 (1.9 %) of 20,432 childbearing patients with

recurrent miscarriage, and they found uncompensated chromosomal abnormalities

in four cases (1 %) out of this group. Uncompensated abnormalities occur in only

about 12 % of abortions with structural chromosomal abnormalities (in 4 % of total

pregnancies involved), and in almost half of the abortion cases, no chromosomal


Most Investigated Causes and Risk Factors of Recurrent Miscarriage


abnormalities can be detected. In the remaining cases, numerical CAs were found

(Desjardins and Stephenson 2012; Kochhar and Ghosh 2013). In light of these facts,

these authors question the necessity of routine chromosomal testing of parents, in

accordance with other researchers (Branch et al. 2010; Tang and Quenby 2010).

Therefore, it is likely that structural chromosomal abnormalities are rarely the cause

of repeated, consecutive abortions.


Anatomical Factors

Malformations resulting from the impaired fusion of the Mullerian duct (the most

common forms are subseptated, septated and bicornuate uterus) occur in approximately 4 % of patients with normal obstetric history whereas in 8 % of patients with

recurrent miscarriage (Sugiura-Ogasawara et al. 2010). In view of the structural

anomalies of the uterus, their role in the occurrence of abortions seems almost evident, although clinical experiences appear to contradict this. Even together with

these developmental abnormalities, a ratio of 60–70 % successful births can be

achieved in patients with several preceding spontaneous abortions (Acien 1993;

Kirk et al. 1993), and a higher success rate (60–75 %) is not even achieved after

metroplasty (Ayhan et al. 1992; Acien 1993; Fedele et al. 1993). Moreover, after

surgery, infertility emerged in 10–25 % of patients (Fedele et al. 1993). SugiuraOgasawara et al. (2010) found that in women with 2–12 abortions, the live-birth rate

of the first pregnancy following examination was lower than in recurrent miscarriage patients with normal uterine cavities (59.5 % and 71.7 %), although the difference in cumulative birth rates was not significant after three pregnancies (70.8 and

85.5 %). In patients with uterine cavity alterations whose pregnancies ended with

abortion or birth, it was mainly the D/C ratio (septum length/remaining uterine cavity length) that showed significant differences, as other authors have also stated

(Salim et al. 2003; Sugiura-Ogasawara et al. 2010). It is also against the primary

causal role of septated uterine cavities that after the complete, controlled hysteroscopic resection of the septum, the rate of abortions hardly changes (34.1 %) and

conception occurs only in 65 % of patients over 3 years (Paradisi et al. 2011). In

mature births after septum resection, the weight of the newborn is significantly

lower than in women with normal uterine cavities (Agostini et al. 2009).

Out of 1000 couples, 50 (5 %) are likely to suffer from RM. Therefore, in 50

women with recurrent miscarriage, the above-mentioned anomalies are expected to

develop in four (8 %) and in 38 (4 %) of the remaining 950 couples. Thus, the question arises: why only approximately every 10th woman with uterus alteration will

develop recurrent miscarriage? It seems plausible that causal factors other than uterine cavity abnormalities are required for the development of habitual abortion.

Moreover, in the presence of uterine abnormalities, 85 % of women with recurrent

miscarriage usually give birth in their third or fourth pregnancies (Jaslow et al.

2010). After their fourth pregnancy, only a small proportion did not give birth,

which is another factor that makes the primary causal role of these alterations doubtful in RM.

Tài liệu bạn tìm kiếm đã sẵn sàng tải về

3 Treatment of Folliculo-Luteal Insufficiency with  Low-­Dosage Corticoid or Combined Corticoid and Clomiphene Citrate Therapy

Tải bản đầy đủ ngay(0 tr)