The Role of Dydrogesterone in the Management of Luteal Phase Defect: A Comprehensive Review.

The luteal phase of the menstrual cycle is a pivotal period characterized by hormonal intricacies that lay the foundation for successful embryo implantation and early pregnancy development. Luteal phase defect (LPD), marked by abnormalities in luteal function, presents challenges that can impede reproductive outcomes. This comprehensive review article explores the role of dydrogesterone in LPD management, elucidating its mechanisms of action, evidence of efficacy, safety profile, and potential in combination therapies. Dydrogesterone, a synthetic progestogen, closely mirrors natural progesterone's actions, effectively supplementing the luteal phase and enhancing endometrial receptivity. Clinical studies demonstrate improved pregnancy rates, extended luteal phase support, and enhanced reproductive outcomes with dydrogesterone supplementation. Its favorable safety profile, minimal side effects, and reduced risk of unwanted hormonal effects contribute to its appeal. Furthermore, dydrogesterone's inclusion in international guidelines solidifies its importance in LPD management. Combination therapies, leveraging synergistic effects, offer a comprehensive approach. As gaps in knowledge persist, future research directions and personalized treatment strategies pave the way for a future where dydrogesterone stands as a beacon of hope in conquering the challenges of LPD and achieving successful reproductive outcomes.

The inadequate corpus luteum.

The corpus luteum is the source of progesterone in the luteal phase of the cycle and the initial two-thirds of the first trimester of pregnancy. Normal luteal function is required for fertility and the maintenance of pregnancy. Progesterone administration is increasingly used during fertility treatments and in early pregnancy to mitigate potentially inadequate corpus luteum function. This commentary considers the concept of the inadequate corpus luteum and the role and effects of exogenous progesterone. Progesterone supplementation does have important beneficial effects but we should be wary of therapeutic administration beyond or outside the evidence base. LAY SUMMARY: After an egg is released a structure is formed on the ovary called a corpus luteum (CL). This produces a huge amount of a hormone called progesterone. Progesterone makes the womb ready for pregnancy but if a pregnancy does not happen the CL disappears after 12-14 days and this causes a period. If a pregnancy occurs, then the pregnancy hormone (hCG) keeps the CL alive and its progesterone supports the pregnancy for the next 6-8 weeks until the placenta takes over and the corpus luteum disappears. That means that if the CL is not working correctly there could be problems getting pregnant or staying pregnant. If a CL is not producing enough progesterone it usually means there is a problem with the growing or releasing of the egg and treatment should focus on these areas. In IVF cycles, where normal hormones are switched off, the CL does not produce quite enough progesterone before the pregnancy test and extra progesterone is needed at this time. In recurrent or threatened miscarriage, however, there is not any evidence that the CL is not working well or progesterone is low. However, there is benefit in taking extra progesterone if there is bleeding in early pregnancy in women with previous miscarriages. This might be because of the effects of high-dose progesterone on the womb or immune system. As changes to the hormone environment in pregnancy may have some life-long consequences for the offspring we have to be careful only to give extra progesterone when we are sure it is needed.

Luteal Phase Support Using Subcutaneous Progesterone: A Systematic Review.

Luteal phase support (LPS) is crucial in assisted reproductive technology (ART) cycles when the luteal phase has been found to be defective. Such deficiency is most likely related to the supraphysiological steroid levels that usually occurr in stimulated cycles which, in turn, could severely affect luteinizing hormone (LH) secretion and function, thereby negatively influencing the luteal phase. A number of different medications and routes have been successfully used for LPS in ART. Although an optimal protocol has not yet been identified, the existing plethora of medications offer the opportunity to personalize LPS according to individual needs. Subcutaneous administration progesterone has been proposed for LPS and could represent an alternative to a vaginal and intramuscular route. The aim of the present systematic review is to summarize the evidence found in the literature concerning the application of subcutaneous progesterone in ARTs, highlighting the benefits and limits of this novel strategy. With this aim in mind, we carried out systematic research in the Medline, ISI Web of Knowledge, and Embase databases from their inception through to November 2020. Randomized controlled trials (RCTs) were preferred by the authors in the elaboration of this article, although case-control and cohort studies have also been considered. According to our findings, evidence exists which supports that, in women with a good prognosis undergoing a fresh in vitro fertilization (IVF) cycle, subcutaneous Pg is not inferior to vaginal products. In the Frozen-thawed embryo transfer (FET) cycle, data concerning efficacy is mixed with an increased miscarriage rate in women undergoing a subcutaneous route in oocyte donor recipients. Data concerning the acceptance of the subcutaneous route versus the vaginal route are encouraging despite the different scales and questionnaires which were used. In addition, a cost-effective analysis has not yet been conducted.

Regulation of Bushen Zhuyun Prescription on Ovarian Endoplasmic Reticulum Stress in Rats with Luteal Phase Defect / 中国实验方剂学杂志

Objective:To investigate the regulatory mechanism of Bushen Zhuyun prescription（BSZYP） on endoplasmic reticulum stress （ERS） in rats with luteal phase defect （LPD） induced by mifepristone. Method:Fifty SD rats were randomly divided into a blank group， a model group， a positive control group （dydrogesterone，0.02 g·kg^-1）， and low-（0.08 g·kg^-1）and high-dose （0.24 g·kg^-1） BSZYP groups. Western blot and Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） were used to detect the mRNA and protein expression levels of immunoglobulin binding protein （BIP）， protein kinase R-like endoplasmic reticulum kinase （PERK）， inositol-requiring enzyme 1 （IRE-1）， activating transcription factor 6 （ATF6）， and C/EBP homologous protein （CHOP）. The enzyme-linked immunosorbent assay （ELISA） was used to detect the serum progesterone （P） and estradiol （E₂） levels. Result:Compared with the blank group， the model group showed the elevated protein expression of BIP， PERK， and CHOP （<italic>P</italic><0.01） and the dwindled mRNA expression of PERK and CHOP （<italic>P</italic><0.05）， while no significant difference was observed in the protein expression of IRE-1 and ATF6， mRNA expression of IRE-1， BIP， and ATF6， and serum E₂ and P levels. Compared with the model group， the positive control group displayed diminished protein expression of CHOP （<italic>P</italic><0.01）， while no significant difference was observed in the protein expression of PERK， IRE-1， BIP， and ATF6， mRNA expression of PERK， IRE-1， BIP， ATF6， and CHOP， and serum levels of E₂ and P. The protein expression of CHOP decreased （<italic>P</italic><0.01） and the mRNA expression of CHOP increased （<italic>P</italic><0.05） in the low-dose BSZYP group， while no significant difference was observed in the mRNA and protein expression of PERK， IRE-1， BIP， and ATF6， and serum E₂ and P levels. In the high-dose BSZYP group， the protein expression of PERK， BIP， and CHOP was down-regulated （<italic>P</italic><0.01）， and the mRNA expression of CHOP was up-regulated （<italic>P</italic><0.01）， while no significant difference was observed in the protein expression of IRE-1 and ATF6， mRNA expression of PERK， IRE-1， BIP， and ATF6， and serum E₂ and P levels. Conclusion:BSZYP can treat LPD by relieving ERS.

Low progesterone levels on the day before natural cycle frozen embryo transfer are negatively associated with live birth rates.

STUDY QUESTION: Are progesterone (P) levels on the day before natural cycle frozen embryo transfer (NC-FET) associated with live birth rate (LBR)? SUMMARY ANSWER: Regular ovulatory women undergoing NC-FET with serum P levels <10 ng/ml on the day before blastocyst transfer have a significantly lower LBR than those with serum P levels >10 ng/ml. WHAT IS KNOWN ALREADY: The importance of serum P levels around the time of embryo transfer in patients undergoing FET under artificial endometrial preparation has been well established. However, no study has analyzed the importance of serum P levels in patients undergoing FET under a true natural endometrial preparation cycle. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study including 294 frozen blastocyst transfers under natural cycle endometrial preparation at a university-affiliated fertility centre between January 2016 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients had regular menstrual cycles and underwent NC-FET with their own oocytes. Only patients who had undergone serum P measurement between 8 am and 11 am on the day before FET were included. Patients did not receive any external medication for endometrial preparation or luteal phase support. Patients were divided into two groups according to serum P levels below or above 10 ng/ml on the day before FET. Univariate analysis was carried out to describe and compare the cycle characteristics with reproductive outcomes. To evaluate the effect of P, a multivariable logistic model was fitted for each outcome after adjusting for confounding variables. MAIN RESULTS AND THE ROLE OF CHANCE: Mean serum P levels on the day before FET were significantly higher in patients who had a live birth compared to those who did not (14.5 ± 7.0 vs 12.0 ± 6.6 ng/ml, 95% CI [0.83; 4.12]). The overall clinical pregnancy rate (CPR) and LBR were 42.9% and 35.4%, respectively. Patients in the higher P group (>10 ng/ml) had a higher LBR (41.1% vs 25.7%: risk difference (RD) 15.4%, 95% CI [5; 26]) and CPR (48.6% vs 33.0%: RD 15.6%, 95% CI [4; 27]). Patients with higher serum P levels on the day before FET (63% of patients) had an improved LBR (odds ratio: 1.05; 95% CI [1.02; 1.09]). Women with serum P levels <10 ng/ml on the day before FET (37% of patients) had significantly higher weights (62.5 ± 9.9 vs 58.1 ± 7.1 kg, 95% CI [1.92; 6.90]) and BMI (22.9 ± 3.6 vs 21.6 ± 2.7 kg/m2, 95% CI [0.42; 2.25]) compared to patients with P levels >10 ng/ml. LIMITATIONS, REASONS FOR CAUTION: The main limitation of our study is its retrospective design. Other potential limitations are the detection of LH surge through urine testing and the inclusion of patients who did and did not undergo preimplantation genetic testing for aneuploidies. The protocol used in our institution for monitoring NC-FET does not look for the onset of progesterone secretion by the corpus luteum, and a slow luteinisation process or delay of corpus luteum function cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS: We provide evidence that a minimum serum P threshold (P >10 ng/ml) might be required for improved reproductive outcomes in NC-FET. This result suggests that there are different mechanisms by which P is produced and/or distributed by each patient. This study also provides an excellent model to evaluate the impact of luteal phase defect through NC-FET. A prospective evaluation to assess whether P supplementation should be individualised according to patient's needs is necessary to support our findings. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used, and there are no competing interests.

[Effect on follicular development and pregnancy outcome treated with acupuncture and moxibustion therapy of Tiaochongren Gushenyuan in patients with luteal phase defect].

OBJECTIVE: To observe the effect of acupuncture and moxibustion therapy of Tiaochongren Gushenyuan on ovulation and embryo implantation in luteal phase defect patients with spleen-kidney yang deficiency. METHODS: A total of 80 patients were randomly divided into an observation group and a control group, 40 cases in each one.In the observation group,acupuncture was applied at Shenting (GV 24), Shenque (CV 8), Guanyuan (CV 4), Qixue (KI 13), Lieque (LU 7), Gongsun (SP 4), Taixi (KI 3), Zusanli (ST 36) and Taichong (LR 3). And moxibustion was given at Taixi (KI 3) using moxibustion box during follicular phase, the stimulation of Taichong (LR 3) was strengthened during ovulatory phase, moxibustion was adopted at Shenque (CV 8) to Guanyuan (CV 4), Zusanli (ST 36) and Taixi (KI 3) during luteal phase. In the control group, acupuncture was applied at Guanyuan (CV 4), Dahe (KI 12), Sanyinjiao (SP 6), Ciliao (BL 32), Zhibian (BL 54) and Shenque (CV 8). Moxibustion was given at Sanyinjiao (SP 6) using moxibustion box during follicular phase, and moxibustion was adopted at Shenque (CV 8) to Guanyuan (CV 4) during luteal phase. The treatment were given every Monday, Wednesday and Friday, and the treatment were stoped during menstrual period in the two groups. Totally 3 menstrual cycle treatment were required, and 3 menstrual cycles were followed up. The pregnancy rate was observed after treatment, the ovulation rate, maximum folliclular diameter and difference of maximum folliclular diameters in ovulatory phase, serum progesterone (P) and basal body temperature (BBT) were compared before and after treatment in the two groups. RESULTS: In the observation group, 6 cases of successful pregnancy during treatment,10 cases in follow-up, the clinical pregnancy rate was 40.0% (16/40). In the control group, 1 case of successful pregnancy during treatment, 5 cases in follow-up, the clinical pregnancy rate was 15.0% (6/40). The clinical pregnancy rate in the observation group was higher than the control group (P<0.05). The ovulation rate after treatment in the observation group was 90.0% (36/40), and the control group was 70.0% (28/40), compared before treatment, the ovulation rates were increased after treatment in the two groups (P<0.05). The observation group was higher than the control group, but there was no significant difference between the two groups (P>0.05). Compared before treatment, the maximum folliclular diameter and difference of maximum folliclular diameters in ovulatory phase, serum P after treatment were improved in the two groups (P<0.05), and the improvements of the observation group were significant compared with the control group (P<0.05). The BBT after treatment were superior to before treatment in the two groups (P<0.05). After treatment, the normal BBT in the observation group was 33 cases, while the control group was 22 cases (P<0.05). CONCLUSION: Acupuncture and moxibustion therapy of Tiaochongren Gushenyuan can promote folliclar development, improve dominant follicle morphology, increase the level of serum P. The therapeutic effect is superior to routine acupuncture in increasing ovulation rate and improving pregnancy outcome.

Association between diminished ovarian reserve and luteal phase deficiency.

OBJECTIVE: To determine the association between biomarkers of ovarian reserve and luteal phase deficiency (LPD). DESIGN: Secondary analysis of a prospective time-to-conceive cohort study. SETTING: Not applicable. PATIENT(S): Women attempting conception, aged 30-44 years, without known infertility. INTERVENTION(S): Measurement of early follicular phase serum levels of antimüllerian hormone, FSH, inhibin B, and E2. MAIN OUTCOME MEASURE(S): The primary outcome was LPD, defined by luteal bleeding (LB) (≥1 day of LB) or a short luteal phase length (≤11 days). RESULT(S): Overall, 755 women provided information on 2,171 menstrual cycles and serum for measurement of at least one biomarker of ovarian reserve. There were 2,096 cycles from 754 women in the LB cohort, of which 40% experienced LB. After adjusting for age, race, previous miscarriages, and previous pregnancies, diminished ovarian reserve (DOR) was not significantly associated with LB. Low early follicular phase FSH levels increased the odds of LB (odds ratio [OR] 1.84; 95% confidence interval [CI] 1.25-2.71), as did high early follicular phase E2 levels (OR 1.59; 95% CI 1.26-2.01). A total of 608 cycles from 286 women were included in the analysis of luteal phase length, of which 13% had a short luteal phase. After adjusting for age, there was no significant association between DOR and a short luteal phase. The risk of a short luteal phase decreased with increasing inhibin B (OR 0.61; 95% CI 0.45-0.81). CONCLUSION(S): Although DOR is not associated with LPD, hormone dysfunction in the early follicular phase may contribute to LPD in women of older reproductive age.

Introduction: Endometrial receptivity: evaluation, induction and inhibition.

Endometrial receptivity is an essential component of the complex process of embryo implantation. Its existence is inferred from the observation that not all embryo transfers result in pregnancy. The endometrium is a unique tissue which undergoes dramatic and rapid changes throughout the menstrual cycle. There appears to be a window of implantation, a time of optimal endometrial receptivity, when embryos are most likely to implant. The assessment of the timing and duration of this window of implantation has been a topic of interest and debate since the 1950s. The existence of the window of implantation led to the development of cycles in which endometrial receptivity is induced with exogenous E2 and P. These cycles are essential to third party parenting and frozen embryo transfers and have therefore become a common part of the practice of assisted reproduction.

Effect on follicular development and pregnancy outcome treated with acupuncture and moxibustion therapy of in patients with luteal phase defect / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture and moxibustion therapy of on ovulation and embryo implantation in luteal phase defect patients with spleen-kidney deficiency.@*METHODS@#A total of 80 patients were randomly divided into an observation group and a control group, 40 cases in each one.In the observation group,acupuncture was applied at Shenting (GV 24), Shenque (CV 8), Guanyuan (CV 4), Qixue (KI 13), Lieque (LU 7), Gongsun (SP 4), Taixi (KI 3), Zusanli (ST 36) and Taichong (LR 3). And moxibustion was given at Taixi (KI 3) using moxibustion box during follicular phase, the stimulation of Taichong (LR 3) was strengthened during ovulatory phase, moxibustion was adopted at Shenque (CV 8) to Guanyuan (CV 4), Zusanli (ST 36) and Taixi (KI 3) during luteal phase. In the control group, acupuncture was applied at Guanyuan (CV 4), Dahe (KI 12), Sanyinjiao (SP 6), Ciliao (BL 32), Zhibian (BL 54) and Shenque (CV 8). Moxibustion was given at Sanyinjiao (SP 6) using moxibustion box during follicular phase, and moxibustion was adopted at Shenque (CV 8) to Guanyuan (CV 4) during luteal phase. The treatment were given every Monday, Wednesday and Friday, and the treatment were stoped during menstrual period in the two groups. Totally 3 menstrual cycle treatment were required, and 3 menstrual cycles were followed up. The pregnancy rate was observed after treatment, the ovulation rate, maximum folliclular diameter and difference of maximum folliclular diameters in ovulatory phase, serum progesterone (P) and basal body temperature (BBT) were compared before and after treatment in the two groups.@*RESULTS@#In the observation group, 6 cases of successful pregnancy during treatment,10 cases in follow-up, the clinical pregnancy rate was 40.0% (16/40). In the control group, 1 case of successful pregnancy during treatment, 5 cases in follow-up, the clinical pregnancy rate was 15.0% (6/40). The clinical pregnancy rate in the observation group was higher than the control group (0.05). Compared before treatment, the maximum folliclular diameter and difference of maximum folliclular diameters in ovulatory phase, serum P after treatment were improved in the two groups (<0.05), and the improvements of the observation group were significant compared with the control group (<0.05). The BBT after treatment were superior to before treatment in the two groups (<0.05). After treatment, the normal BBT in the observation group was 33 cases, while the control group was 22 cases (<0.05).@*CONCLUSION@#Acupuncture and moxibustion therapy of can promote folliclar development, improve dominant follicle morphology, increase the level of serum P. The therapeutic effect is superior to routine acupuncture in increasing ovulation rate and improving pregnancy outcome.

Luteal phase support for documented failure of placental steroidogenesis: A case report.

OBJECTIVE: To report a case of a habitual aborter that had a pregnancy reach near term and successfully delivered a viable female infant. DESIGN: Report of a unique case of a G10P1 that was successfully able to maintain a pregnancy by maintaining serum levels of estradiol and progesterone at or above 200 pg/dL and 25 ng/dL respectively. This case provides a benchmark for exogenous support of estradiol and progesterone throughout pregnancy. SETTING: A private advanced reproductive center. PATIENT: 39-year-old G10P1091 diagnosed to have antiphospholipid syndrome but continued to have continuous miscarriages despite accepted treatment. In addition, 8 products of conception were sent for cytogenetic testing and all were found to be normal. INTERVENTIONS: Examination, laboratory studies, imaging, clinical judgment, and knowledge of previous treatment failures were used to guide the treatment of this patient. Fertility was achieved with continuous supplementation of progesterone, estrogen, LMW-heparin, and prednisone. MAIN OUTCOME MEASURE: Delivery of viable infant. RESULTS: This advanced reproductive age woman had three subsequent pregnancies. While compliant with our prescribed protocol, the patient successfully carried two pregnancies to viability. CONCLUSION: Clinicians should be alert to the possibility of a luteal phase defect when a patient presents with recurrent fertility problems and multiple spontaneous abortions.

Altered expression of hormone receptor, integrin ß3 and pinopode in the endometrium of luteal phase defect women.

OBJECTIVE: To invistigate estrogen receptor (ER), progesterone receptor (PR), integrin ß3, and pinopode expression in luteal phase deficiency (LPD) women. METHODS: There were 52 nulligravidas consecutive infertile patients undergoing a routine assistant reproduction consultation included in this study. An endometrial biopsy sample was randomly obtained between days 4 and 10 of the luteal phase. Endometrial morphology was examined with scanning electron microscopy. Expressions of ER, PR, integrin ß3 were determined in the endometrium of LPD patients with immunohistochemistry. RESULTS: The incidence of LPD was 15.3% (8/52) in this study. On day luteinizing hormone (LH) surge + 9∼LH + 10, noted regressing pinopodes resembling a day LH + 7∼LH + 8 in the endometrium of the control group. The expressions of ER and PR in glandular epithelium were significantly increased in endometrium of LPD than that in the control group (p < 0.05). In contrast, there was a statistically significant decrease expression of the integrin ß3 in women from the group of LPD (p < 0.05). CONCLUSION: The altered expression of ER and PR may be associated with the expression variation of integrin and pinopode formation in endometrium of LPD women. This alteration may imply the association of low rates of cycle fecundity and high rates of embryonic loss in LPD women.

Endocrine dysfunction and recurrent spontaneous abortion: An overview.

Miscarriage is the spontaneous loss of a fetus before it is viable, occurring at a rate of 15-20%. Recurrent spontaneous abortion (RSA) or habitual miscarriage is defined as repeated occurrence of 3 or more miscarriages before 20(th) week of gestation accounting for the most common complication of early pregnancy in humans. Various etiological factors responsible for recurrent miscarriage are anatomical, genetical, endocrinological, immunological, and infectious. The endocrinological abnormalities may be polycystic ovarian syndrome, hyperprolactinemia, luteal phase defect, thyroid dysfunction, diabetes, or hyperandrogenism contributing to recurrent pregnancy loss. In the present article, the role of endocrinological disorders in patients with RSA has been reviewed. The article search was done using electronic databases, Google scholarly articles, and PubMed based on different key words. We have further combined the searches and made grouping as per various endocrine abnormalities, which might be responsible to cause spontaneous loss of fetus.

B ushen Zhuyun Reic pe improves them orphology of the gonad axis of rats with mfi epristone-induced luteal phase defect / 医学研究生学报

Objective The purpose of this study was to construct a rat model of luteal phase defect ( LPD) with mifepristone ( RU486 ) and investigate the improving effect of Bushen Zhuyun Recipe ( BZR ) on the gonad axis morphology of the LPD rat . Meth ods We established rat models of LPD by giving RU486 at 1 mL/100 g followed by treatment with BZR at 0.4 (medium dose) or 1.2 mL/100g ( high dose ) .Then we observed the changes of morphology of the hypothalamus pituitary ovary uterus . Results Electron microscopy revealed hypothalamic mitochondria vacuolization , degranulation of rough endoplasmic reticulum , dissolved nuclear membrane , and decreased secretory granules , while light microscopy exhibited slightly reduced density of pituitary cells , karyopyknosis of some of the cells ,and cytoplasmic vacuolization in the model rats .Electron microscopy also showed obvious shrinkage of cell nuclei , chromatin condensation , disordered cell arrangement , swelling mitochondrial cavity , and formation of vacuoles in the pituitary anterior lobe, while light microscopy also manifested increased ovarian follicular atresia , reduced granule cell layers and corpora lutea , thinned endometrial layers , decreased uterine glands of the tube wall , reduced glandular cavity , and increased interstitial collagen fibers .After BZR treatment, the number and volume of corpora lutea were increased , the granulosa cell layer and endometrial layer thickened , the number of uterine glands increased , and the gland cavity expanded . Conclusion The axes of the hypothalamus , pituitary, uterus,and o -varian were morphologically changed in the RU 486-induced rat models of LPD, while BZR could improve these changes .

Endocrine basis for recurrent pregnancy loss.

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.

Retrospective Analysis of Zhu Yun Pill in Treating 133 Cases of Infertility due to LPD / 中华中医药杂志

Objective: To investigate the effects of Zhu Yun Pill(ZYP) in the treatment of infertility due to luteal phase defect(LPD).Methods: 163 infertility patients due to LPD were randomly divided into three groups in terms of ZYP group,progesterone group and combination group(ZYP and progesterone).Then the therapeutic efficacy was judged by the pregnancy rate(PR),endometrial biopsy,the level of serum hormone and basal body temperature before and after the treatment.Result: 40 women were pregnant in ZYP group(cure rate,33.33%),8 in the progesterone group(cure rate,26.67%) and 9 in the combination group(cure rate, 69.23%).The symptomatic amelioration and total effective rate of ZYP group were obviously higher than single exogenous progesterone group(P

Expression of Leukemia Inhibitory Factor (LIF) in the Clomiphene Citrate Treated Infertile Women with Luteal Phase Defect / 대한산부인과학회잡지

OBJECTIVE: Although the regulation of implantation is not clearly understood, recent studies have revealed that many cytokines and growth factors play an essential role in preimplantation endometrial development. Among the cytokines, the expression of leukemia inhibitory factor (LIF) is absolutely essential for implantation, although its precise role is not fully understood. Clomiphene citrate is most commonly used drug in the treatment of infertility, but pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to the antiestrogenic effect of it on the cervical mucus and endometrium. The our purpose was to evaluate the endometrial expression of LIF in clomiphene citrate treated infertile women with luteal phase defect and association of clomiphene citrate and unsatisfactory endometrial development. METHODS: The endometrial samples from women with luteal phase defect (n=27) were examined. The endometrial tissue was obtained during secretory phase in 5 cases, and during proliferative phase in 6 cases without clomiphene citrate treatment. In 16 cases, the endometrial tissue was obtained by biopsy during secretory phase after clomiphene citrate treatment. Immunohistochemical staining was performed for LIF in the endometrial tissues. And then the expression of LIF was compared between clomiphene citrate treatment group and no treatment group during secretory phase, and secretory and proliferative phase were compared in the no treatment group. RESULTS: The endometrial expression of LIF was not significantly different between clomiphene citrate treated group and no treated group (p. value=0.123) and between proliferative phase and secretory phase without clomiphene citrate (p. value=0.306). The expressions of LIF were detected mostly in glandular epithelial cells and not in the stromal cells. CONCLUSION: We demonstrated that LIF was expressed in glandular epithelial cells rather than stromal cells and there was not menstrual cycle dependent difference of endometrial expression of LIF in infertile women with luteal phase defect. And our finding suggested that clomiphene citrate did not affect the secretory phase endometrial expression of LIF in infertile women with luteal phase defect.

Comparison of Expression of Endometrial Prolactin in infertile Women with Luteal Phase Defect According to Clomiphene Citrate Administration / 대한불임학회지

OBJECTIVE Clomiphene citrate is one of the most commonly used drugs in the treatment of infertility, but the pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to its antiestrogenic effect on the endometrium. Endometrial prolactin is considered to be a marker and an inducer of predecidualization that is characteristic of secretory endometrium. The purpose of this study was to evaluate the association of clomiphene citrate and unsatisfactory endometrial differentiation to secretory endometrium by examining the endometrial expression of prolactin in clomiphene citrate-treated infertile women with luteal phase defect. METHODS: The endometrial samples from infertIle women wIth luteal phase defect (n=27) were examined. Five cases during secretory phase and six cases during proliferative phase were obtained by biopsy. Sixteen cases were obtained by biopsy during secretory phase after clomiphene citrate treatment. By immunohistochemical staining for prolactin, all obtained endometrial tissues were examined. The differences in the endometrial expression of prolactin were evaluated between proliferative phase and secretory phase, and between clomiphene citrate treated group and no treatment group during secretory phase. RESULTS: The staining of endometrial prolactin was significantly more intense in the glandular epithelial cells and stromal cells in the secretory endometrium than in the proliferative endometrium. The glandular expression of prolactin in the secretory endometrium was not significantly different between the clomiphene citrate-treated group and no treatment group (p=0.719), but the staining of prolactin in the stromal cells was significantly less intense in the clomiphene citrate-treated group than no treatment group (p=0.019). CONCLUSION: in this investigation, we demonstrated that the endometrial stromal expression of prolactin in the secretory phase was significantly lower in the clomiphene citrate-treated group campared with no treatment group in infertile women with luteal phase defect. And our finding suggests that clomiphene citrate may have an adverse effect on the endometrial predecidualization in infertile women.

Analysis of Histological Findings and Estrogen and Progesterone Receptor Status in Luteal Phase Defect Caused by Delayed Ovulation and Clomiphen Treatment

Luteal phase defect (LPD) is an ovulatory disorder of considerable clinical importance that leads to delayed endometrial maturation and inadequate endometrium for blastocyst implantation. This disorder is implicated in infertility and recurrent spontaneous abortion. We analyzed the endometrial histological maturation, and the estrogen receptor(ER) and progesterone receptor(PR) status in patients with unexplained delayed ovulation, and in patients with ovulation induction by clomiphen citrate. The purpose of this study was to determine whether the length of the follicular phase influences the endometrial histological maturation and the hormonal receptor status, and to know the effect of clomiphen citrate on the endometrium. In the delayed ovulation group, the endometrium was characterized by an irregular outpouching and dilated lumina of the glands, a decreased secretory activity and predecidualization, and a decreased number of granulocytes in the stroma. In the clomiphen citrate-ovulation induction group, glandular proliferation was markedly diminished with poorly convoluted and narrow glands, secretory activity was decreased, stroma was undecidualized, and there was an absence of granulocytes. ER expression was increased in the glandular epithelium in the delayed ovulation group, and both ER and PR expressions were markedly decreased in the glandular epithelium and stromal cells in the ovulation induction group. Endometrial maturation and differentiation may be diminished by increased estrogenic and relatively deficient progesterone effects in patients with delayed ovulation. The hormonal receptor status might also be influenced by hormonal changes. Clomiphen citrate successfully induced ovulation in patients with delayed ovulation, however, endometrial proliferation and maturation were markedly suppressed. This might be related to the lower pregnancy rate and higher abortion rate in patients with clomiphen citrate induced ovulation.