Pregnancy following GnRH agonist therapy of uterine leiomyoma obstructing a single Fallopian tube

Several studies have shown that gonadotrophin-releasing hormoneanalogue (GnRHa) offers a promising medical approach in thetreatment of uterine leiomyomas. Medical management is veryimportant especially when fertility is desired. We report ona case with mechanical infertility, in which the right tubewas obstructed by cornual myoma and the left tube was resecteddue to a ruptured ectopic pregnancy. The myoma was reduced insize by GnRHa treatment and the patient subsequently conceived.     

Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. European Cetrorelix Study Group

In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.     

Combined oestrogen--progestin treatment of vaginal haemorrhage following gonadotrophin-releasing hormone agonist therapy of uterine myomas

Three pre-menopausal women with uterine myomas were treatedwith leuprolide acetate depot and experienced profuse vaginalbleeding 7–11 weeks after initiation of treatment, despiteprofound oestradiol suppression. In each case, leuprolide therapywas discontinued and the women were treated with combinationoral contraceptives and ferrous sulphate. Vaginal bleeding ceasedwithin 24–48 h of oral contraceptive treatment in allwomen. Haemoglobin concentrations were restored to normal valuesand all women underwent definitive surgical treatments after4–6 weeks of oral contraceptive treatment without theneed for homologous blood transfusion. The final pathology reportrevealed focal necrosis of submucous myomas in all cases.     

Plasma luteinizing hormone bioactivity and immunoactivity in ovariectomized rats treated with a long-acting agonist of luteinizing hormone releasing hormone.

The dose response of a luteinizing hormone releasing hormone (LHRH) agonist in rats with high endogenous gonadotrophin levels was determined. Female rats were ovariectomized and injected with 0.3 microgram (group B), 3.2 micrograms (group C), 32 micrograms (group D) and 320 micrograms (group E) of a slow-releasing microcapsule preparation of the LHRH agonist D-Trp 6-LHRH. Control ovariectomized rats (group A) remained untreated. Plasma luteinizing hormone (LH) concentrations were measured by radioimmunoassay (RIA) before the LHRH agonist injection as well as 5, 15 and 30 days thereafter. Furthermore, LH bioactivity was determined by an in vitro rat LH bioassay in order to evaluate changes in bioactivity after administration of LHRH agonist. In control rats, plasma LH concentrations increased to 4.8 +/- 1.3 ng/ml on day 5, reaching peak levels of 9.9 +/- 1 ng/ml on day 30. In contrast to the control group, those rats which received 320 micrograms of LHRH agonist did not show any increase. Rats which received intermediate doses (groups C and D) tended to maintain levels of LH halfway between group A and group E during the first 15 days of treatment. Thereafter LH concentrations were similar to the untreated control group. The course of the LH concentrations during treatment measured by bioassay (BA) showed a similar pattern to the LH concentrations measured by RIA. The BA/RIA ratio was similar in all groups.     

Patterns of hormonal response to the GnRH agonist leuprolide in brothers of women with polycystic ovary syndrome: a pilot study

BACKGROUND: The aim of this study was to evaluate the effect of a single dose of leuprolide acetate on gonadotrophin and gonadal steroid secretion in brothers of women with polycystic ovary syndrome (PCOS), in order to assess P450c17alpha activity. An oral glucose tolerance test (OGTT) and a lipid profile were also performed. METHODS: Twenty-two unrelated brothers of women with PCOS (PCOS(b)) and 14 brothers of normal cycling women (C(b)), matched for age, underwent a leuprolide acetate test (10 microg/kg s.c.) and an OGTT with measurement of circulating concentrations of gonadotrophins, steroid hormones, glucose, insulin and lipids. RESULTS: Clinical and basal hormonal parameters were similar in both groups. After leuprolide administration, PCOS(b) exhibited a significant increase of 17alpha-hydroxyprogesterone (17-OHP) compared to C(b) (P<0.05). However, only 45% of PCOS(b) showed a supranormal increase of 17-OHP (2 SD above the respective control group mean values, P<0.003) with a normal gonadotrophin response (group 1). The other 55% of the PCOS(b) exhibited a normal 17-OHP response to the analogue (group 2). However, in group 2, basal steroid concentrations did not show a uniform pattern: six of the PCOS(b) exhibited high basal androstenedione (2 SD above the respective control group mean values), three were very similar to C(b), and the other three presented lower basal testosterone concentrations (2 SD below the respective control group mean values) than those observed in C(b). CONCLUSIONS: This study shows that different responses to leuprolide in PCOS brothers make evident the heterogeneity of this syndrome in which P450c17alpha activity could be involved.     

Endocrinology: A comparison between a standard and reduced dose of D-Trp-6-luteinizing hormone-releasing hormone administered after pituitary suppression for in-vitro fertilization

A randomized prospective study was undertaken to compare lowand standard luteinizing hormone-releasing hormone agonist (LHRHa)dosage used in combination with gonadotrophins in ovarian stimulationfor in-vitro fertilization (IVF). A total of 42 ovulatory patientswith mechanical infertility were administered 0.5 mg/day LHRHa(Decapeptyl) from day 21 of their cycles for 14 days. Followingdown-regulation, patients were randomly allocated to continuewith the same dose of LHRHa (22 patients, group A) or to receivea lower dose of 0.1 mg/day LHRHa (20 patients, group B) duringfolliculogenesis. Luteal phase was supported by daily i.m. progesterone(50 mg) injections and human chorionic gonadotrophin (HCG; 1500IU) every 4 days. Ovarian response, human menopausal gonadotrophin(HMG) dosage used for induction of ovulation, evidence of prematureluteinization, and clinical and laboratory IVF outcome, werecompared between groups A and B. The two groups were comparablein respect of: age (32.6 ± 0.7 and 33.0 ± 0.9years), HMG dosage (33.0 ± 1.6 and 36.0 ± 2.5ampoules), day of HCG (11.2 ± 0.3 and 12.2 ± 0.4),oocytes/patient (13.3 ± 1.0 and 12.9± 1.3), fertilizationrate (68.5 and 65.2%), cleavage rate (95% for both), pregnancy/embryotransfer (32 and 35%) and implantation rate (10.8 and 10.5%),for groups A and B respectively. There was no evidence of prematureluteinization or luteolysis in either group. It was concludedthat lowering the dose of LHRHa to 0.1 mg/day during folliculogenesishad no adverse effect on ovarian response or clinical results.However, it had no advantage in reducing the HMG dose used forovulation induction.     

Pathological evaluation of uterine leiomyomas treated with gonadotropin-releasing hormone agonist (GnRH-a) therapy: role of mast cells and a possible mechanism of GnRH-a resistance in leiomyomas

Gonadotropin-releasing hormone agonist (GnRH-a) therapy is frequently applied to reduce the volume of uterine leiomyomas (UL). In addition, the possible relationship between mast cells (MC) within UL and the development of UL has been suggested, but the role of MC in UL remains to be determined. UL with or without GnRH-a therapy in 121 premenopausal patients were reviewed. The number of MC was evaluated between the two groups, immunohistochemistry was done for insulin-like growth factor-I (IGF-I), and the association between the IGF-I immunoreactivity in UL and the GnRH-a therapy was analyzed. The number of MC significantly increased in UL in GnRH-a therapy, while IGF-I immunoreactivity was significantly reduced in smooth muscle cells of these UL. Furthermore, IGF-I immunoreactivity in MC was inversely correlated with the size reduction rate of UL in GnRH-a therapy. Although GnRH-a therapy is considered to reduce the size of UL transiently, the regression of UL was in part hampered by the increased IGF-I secretion from the increased MC after GnRH-a therapy. Therefore, the more the IGF-I secretion from MC in UL increases, the less effective the GnRH-a therapy is on the size reduction of UL. Thus, the present study may provide an explanation of the possible mechanism of GnRH-a resistance in UL.     

Endocrinology: Pituitary responsiveness to gonadotrophin-releasing hormone agonist stimulation: a dose--response comparison of luteinizing hormone/follicle-stimulating hormone secretion in women with polycystic ovary syndrome and normal women

In polycystic ovary syndrome (PCOS), the mechanism responsiblefor abnormal gonadotrophin secretion, elevated serum luteinizinghormone (LH) and normal or low follicle-stimulating hormone(FSH) concentrations has not been elucidated. One proposed mechanism,as suggested by previous studies, is an augmented sensitivityof pituitary LH release and a corresponding insensitivity ofpituitary FSH release to gonadotrophin-releasing hormone (GnRH)agonist stimulation. This study was designed to further comparegonadotrophin responses to GnRH agonist stimulation within andbetween individual patients in a dose—response manner.Each of six PCOS and six normal ovulatory women was administereda single s.c. injection of the GnRH agonist [(imBzl)D-His⁶,Pro⁹-NEt]-GnRH (D-His) at a dose of 0.01, 0.1, 1 and 10 µg/kgon four separate occasions. Blood samples were obtained overa 72 h period following D-His administration. Gonadotrophinresponses were measured by (i) the maximal rise from pretreatmentbaseline values (Amax); (ii) the maximal percentage change frombaseline (%Amax); and (iii) the integrated response (mean ofthe cumulative sum of deviations from baseline). Within-groupand between-group dose—responses were compared by two-factoranalysis of variance and further characterized using the ‘Flexifit’computer program. Our results showed that in both groups, progressiveincreases of LH and FSH occurred following D-His at doses of0.01 and 0.1 µg/kg. Further increases beyond the 0.1 µg/kgdose were not observed. In PCOS women, Amax and integrated responsefor LH were significantly greater than those of normal subjectsat each dose tested. %max of LH was significantly lower in PCOS,reflecting higher pretreatment baseline LH concentrations inthis group. FSH responses to D-His were not significantly differentbetween PCOS and normal women. In PCOS, within-group comparisonsfailed to reveal a uniform pattern of LH dose—response.In contrast, LH integrated response curves were homogeneousamong individual normal women, as were the corresponding curvesfor FSH among both PCOS and normal women. These findings indicatethat PCOS patients exhibit greater LH responsiveness to GnRHagonist on a per-dose basis than that of normal women. Amongindividual PCOS patients, inconsistent dose—response patternsof LH release underscore the subtle variability of LH secretionamongst women with this disorder.     

Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review

BACKGROUND: Uterine leiomyomas are extremely common and a major cause of pelvic pain, bleeding, infertility, and the leading indication for hysterectomy. Familial and epidemiological studies provide compelling evidence that genetic alterations play an important role in leiomyoma development. METHODS: Using Affymetrix U133A GeneChip we analysed expression profiles of 22,283 genes in paired samples of leiomyoma and adjacent normal myometrium. We compared our results with previously published data on gene expression in uterine leiomyoma and identified the overlapping gene alterations. RESULTS: We detected 80 genes with average differences of > or = 2-fold and false discovery rates of < 5% (14 overexpressed and 66 underexpressed). A comparative analysis including eight previous gene expression studies revealed eight prominent genes (ADH1, ATF3, CRABP2, CYR61, DPT, GRIA2, IGF2, MEST) identified by at least five different studies, eleven genes (ALDH1, CD24, CTGF, DCX, DUSP1, FOS, GAGEC1, IGFBP6, PTGDS, PTGER3, TYMS) reported by four studies, twelve genes (ABCA, ANXA1, APM2, CCL21, CDKN1A, CRMP1, EMP1, ESR1, FY, MAP3K5, TGFBR2, TIMP3) identified by three studies, and 40 genes reported by two different studies. CONCLUSIONS: Review of gene expression data revealed concordant changes in genes regulating retinoid synthesis, IGF metabolism, TGF-beta signaling and extracellular matrix formation. Gene expression studies provide clues to the relevant pathways of leiomyoma development.     

Acceptability and patterns of uterine bleeding in sequential trimegestone-based hormone replacement therapy: a dose-ranging study

Trimegestone is a norpregnane progestogen which is being developed in combination with oral oestradiol as postmenopausal hormone replacement therapy (HRT). In this multicentre dose-ranging study using randomized parallel groups, four doses of trimegestone were used to compare data on the patterns of uterine bleeding, the endometrial histology, and the control of menopausal symptoms in 203 women who completed treatment for 6 months. The treatment consisted of micronized oestradiol (2 mg/day) and one of four doses of trimegestone, which was administered sequentially for days 15-28 of the treatment cycle. Higher doses of trimegestone were associated with later onset of bleeding, which was lighter and of shorter duration than that observed with lower doses. The variability of the day of onset of bleeding in individual women was greater when bleeding occurred before the end of the progestogen phase (early bleeders) than when it occurred afterwards (late bleeders). All women enrolled in the study experienced good control of menopausal symptoms, with minimal progestogenic adverse effects, there being no statistically significant difference between the four dose groups.     

GnRH agonist as luteal phase support in assisted reproduction technique cycles: results of a pilot study

BACKGROUND: The aim of the study was to investigate whether intranasal (IN) administration of a GnRH agonist could provide luteal support in IVF/ICSI patients. METHODS: Controlled ovarian hyperstimulation (COH) was performed using hMG/FSH and a GnRH antagonist. Patients were then randomly allocated to either 10,000 IU hCG, followed by vaginal administration of micronized progesterone (3x 200 mg/day) (group A), or 200 microg IN buserelin followed by either 100 microg every 2 days (group B), or 100 microg every day (group C), or 100 microg twice a day (group D), or 100 microg three times a day (group E). Luteal support was continued for 15 days. RESULTS: Twenty-three patients were randomized. Groups B and C were discontinued prematurely in view of the short luteal phase. The luteal phase was significantly shorter in groups B, C and D, whereas group E was comparable with group A, 13.5 and 13.0 days, respectively. In the mid-luteal phase, median progesterone levels were significantly lower in groups B, C and D, whereas group E was comparable with group A, 68.9 and 98.0 ng/ml, respectively. Estradiol (E2) was significantly reduced in groups B and D but sustained in group E. In the hCG group, LH levels were undetectable (<0.1 IU/l), whereas LH was detectable and significantly higher in groups C, D and E. Two pregnancies were obtained in the hCG group (two of five), one ectopic and one ongoing. Three pregnancies were obtained in group E, one miscarriage and two ongoing twin pregnancies (three of five). CONCLUSION: IN administration of buserelin may be effective in triggering follicular maturation and providing luteal phase support in patients undergoing assisted reproduction techniques (ART).     

The influence of hormone replacement therapy on skin ageing: a pilot study.

OBJECTIVES: We studied the effect of hormonal treatment on skin ageing in menopausal women. METHODS: Twenty-four patients (45-68 years; mean age, 54.9 years) without hormone treatment for at least 6 months were included. Patients were assigned to three therapy groups: 1, oestrogen only (Estraderm TTS 50) (n=6); 2, transdermal oestrogen and progesterone (Estraderm TTS 50 and 0.4 mg progesterone vaginal suppository) (n=7); and 3, oral oestrogen and progesterone (2 mg Progynova and 0.4 mg progesterone vaginal suppository) (n=8). One group without therapy was included as a control group (n=3). Treatment was continued for 6 months. Three patients, one from group 2 and two from group 3, discontinued therapy before the study endpoint. The following skin parameters were measured at monthly intervals during treatment: skin surface lipids, epidermal skin hydration, skin elasticity and skin thickness. Concomitant clinical evaluation included a subjective clinical evaluation form, a patient questionnaire and laboratory tests for oestradiol, progesterone and follicle stimulating hormone. RESULTS: Mean levels of epidermal skin moisture, elasticity and skin thickness were improved at the end of treatment based on both subjective and objective evaluation in patients with hormone replacement therapy (HRT). Skin surface lipids were increased during combined HRT, which may reflect stimulatory effects of the progestagen component on sebaceous gland activity, while oestrogen alone has a sebum-suppressive action. In the HRT groups, the questionnaire for climacteric complaints demonstrated significant improvements, while laboratory tests showed increases in oestradiol and progesterone and decreases in FSH. CONCLUSIONS: HRT with the mentioned regimes significantly improved parameters of skin ageing.     

Endocrinology: Long-term medical therapy for leiomyomata uteri: a prospective, randomized study of leuprolide acetate depot plus either oestrogen--progestin or progestin 'add-back' for 2 years

Treatment of women with leiomyomata with gonadotrophin releasinghormone agonists (GnRHa) for >6 months is not recommendedbecause of concerns regarding adverse sequelae of prolongedhypoestrogenism. It has been postulated that addition of low-dosesex steroids to GnRHa treatment, i.e. ‘add-back’therapy, may avert some of these adverse effects (acceleratedbone resorption, vasomotor flushes) without altering the efficacyof GnRHa therapy. To evaluate the effects of long-term GnRHatherapy on uterine size, bleeding patterns, bone mass and lipids,51 pre-menopausal women with leiomyomata were treated with theGnRHa leuprolide acetate depot, 3.75 mg every 4 weeks for 2years. After 3 months of leuprolide therapy, the women wererandomized to receive either low-dose continuous oestropipate,0.75 mg daily, plus cyclic norethindrone, 0.7 mg on days 1—14each month (the oestrogen–progestin add-back group) orhigher-dose norethindrone, 10 mg daily (the progestin add-backgroup), for the remaining 21 months. Mean uterine volume decreasedby 40% in both treatment groups during the first 3 months onleuprolide treatment. There was no significant change in uterinesize following oestrogen–progestin add-back. However,mean uterine volume in the progestin add-back group increasedto 87% of pre-treatment size by treatment month 12 and 95% ofpre-treatment size by treatment month 24. Mean bone densityof the lumbar spine as measured by dual X-ray absorptiometrydecreased significantly by 2.6% during the first 3 months inall patients, but did not change significantly following steroidadd-back in both treatment groups during the final 21 treatmentmonths. There were parallel and significant increases in meanhaematocrits (Hct) of 4.8% in the oestrogen—progestingroup and 7.8% in the progestin group over the 2-year treatmentperiod. Mean serum high density lipoprotein (HDL) cholesterolconcentration was unchanged in the oestrogen—progestinadd-back group but decreased by 36% in women receiving progestinadd-back. By 6 months after completion of treatment, mean uterinevolume, leiomyoma-related symptoms, Hct and bleeding patternshad returned to pre-treatment values. Thus, the oestrogen—progestinadd-back regimen was superior or equal to the progestin add-backregimen in all safety and efficacy parameters studied; the latterregimen was associated with regrowth of myomatous uterine volumeand with marked depression of cardio-protective HDL cholesterolconcentrations. One 50 year old woman in the oestrogen—progestingroup developed a leiomyosarcoma which was suspected by sonographicchanges in leiomyoma appearance and was thought to be unrelatedto treatment. In conclusion, GnRHa plus oestrogen—progestinadd-back therapy may provide a long-term (i.e.>6 month) medicaltreatment option in women with leiomyomata.     

A morphometric study of the uterine glandular epithelium in women with premature ovarian failure undergoing hormone replacement therapy.

In this study we examined the fine structure of the human glandular epithelium in women with idiopathic ovarian failure in artificial cycles produced by two different types of hormone replacement therapy (oestradiol valerate orally and either intramuscular injection of progesterone or progesterone via vaginal pessary), both of which had been claimed to be capable of supporting successful implantation. Biopsies were performed on day 19 of the artificial cycle. A variety of sterological probes were used to quantify the structural characteristics of these cells and the results obtained were compared with those from normal fertile subjects biopsied on days 2 and 5 after the luteinizing hormone (LH) surge. The glandular epithelial cells from the vaginal group had a less elaborate secretory apparatus when compared with the intramuscular group or with LH + 5 controls. Many of the features of the vaginal group suggested a continued oestrogenic influence, while the intramuscular group seemed to be more advanced than LH + 5.     

Transfer of frozen-thawed embryos in artificially prepared cycles with and without prior gonadotrophin-releasing hormone agonist suppression: a prospective randomized study

Transfer of frozen–thawed embryos is usually carried outin a natural cycle or in a programmed cycle in which the endometriumis exogenously stimulated following down-regulation of the hypophysis.To analyse the possibility that the programmed cycle for embryotransfer can still be hormonally manipulated without the useof gonadotrophin-releasing hormone agonist (GnRHa) we have conducteda prospective randomized study that compared the outcome offrozen–thawed embryo transfer cycles using micronized17ß-Oestradiol and micronized progesterone preparationswith and without the concomitant use of GnRHa. One hundred andsix patients were randomly divided into two groups. In groupA (53 patients) 4 mg/day of micronized 17ß-oestradiolwas initiated following down-regulation of hypophysis. In groupB (53 patients) oestrogen stimulation started on day 1 of thecycle without prior pituitary down-regulation using a dose of6 mg/day for 7 days. In both groups, micronized progesteronein a dose of 900 mg/day was administered vaginally after atleast 12 days of oestrogen stimulation. Embryo transfer embryotransfer took place 48-72 h thereafter according to the cryopreservedembryonic stage. Overall, none of the patients had any folliculardevelopment and only one cycle in group B had to be cancelledbecause of premature progesterone secretion. The two groupsdid not differ in age (31 ± 5.6 and 31 ± 5.0 years),number of embryos transferred per patient (3.4 ± 1.2and 3.3 ± 1.0), and day of progesterone initiation (15± 2.2 and 15 ± 1.9 for groups A and B respectively).The endometrial thickness on the day of progesterone initiationwas comparable in both groups (11 ± 1.6 and 10 ±1.6 mm for groups A and B respectively). Similarly, the pregnancyrate per embryo transfer and implantation rate in group A (26.4%and 9.5%) were comparable to those of group B (21.1% and 9%).These results indicate that programmed cycles can be successfullyapplied by administering a high dose of micronized 17ß-oestradiolstarting on day 1 of the cycle. Compared to GnRHa programmedcycles, this approach is simpler, more convenient for both thepatient and medical staff, and results in a similar successrate at a lower cost.     

Risk of benign gynaecological diseases and hormonal disorders according to responsiveness to ovarian stimulation in IVF: a follow-up study of 8714 women

BACKGROUND: Over the past decade, attention has been focused increasingly on the long-term health effects of IVF in women. Assuming that hormonal changes due to stimulation regimens for IVF are strongest among 'high' responders, we evaluated whether responsiveness to ovarian stimulation in IVF is predictive of the risk of benign gynaecological disorders >12 months after the last IVF cycle. METHODS: A nationwide historical cohort study of women who underwent IVF treatment was conducted. After a median time of 4.6 years following the last IVF treatment cycle, 8714 cohort members completed a health survey questionnaire that inquired about reproductive variables and the occurrence and age at onset of specific medical conditions including uterine leiomyoma, surgically removed ovarian cysts and thyroid disorders. Detailed data on cause of subfertility and IVF treatment were collected from the medical records. Women were included in the 'high responders' group when on average >/=14 oocytes were retrieved per IVF cycle (n = 1562), in the 'normal responders' group when they had a mean number of 4-13 retrieved oocytes (n = 6033), and in the 'low responders' group when they had a mean number of 0-3 retrieved oocytes per cycle (n = 1119). RESULTS: Among women with a high response to ovarian stimulation, we found a borderline significantly decreased risk of uterine leiomyoma [relative risk (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0] and surgically removed ovarian cysts (RR = 0.6; 95% CI 0.3-1.0) in comparison with 'normal responders'. After OHSS, the age-adjusted RRs were 1.8 (95% CI 0.9-3.8) for having surgically removed ovarian cysts and 1.0 (95% CI 0.4-2.2) for uterine leiomyoma (both not significant). CONCLUSIONS: Despite the small number of events observed, highly elevated risks of gynaecological disorders and hormonal diseases in women undergoing IVF treatment can be excluded based on the present data and this follow-up period. Women with a low response to ovarian stimulation tended to have higher risks of benign gynaecological diseases than high responders.     

Endometrioma of uterine serosa in a woman with mosaic Turner's syndrome receiving hormone replacement therapy: case report

Endometriosis in Turner's syndrome patients has only been reported in five isolated cases. We present here an endometrioma on the uterine serosa and pelvic endometriosis arising in a mosaic Turner's patient receiving hormone replacement therapy (HRT). The 24 year old patient with mosaic Turner's syndrome [45,X; 46,X pseudo dicentric Y (q11.23)], on cyclic HRT after laparoscopic gonadectomy 5 years previously, was found to have an adnexal mass on routine examination. Given her history, due to the fear of a malignant process arising from a potential gonadal remnant, she underwent a laparoscopy and was found to have a 5 cm serosal endometrioma arising on a stalk from the uterine fundal surface as well as pelvic endometriosis. De-novo endometrioma and endometriosis occurred in a mosaic Turner's patient after gonadectomy on cyclic HRT. The presentation was also unusual with a pedunculated endometrioma arising from the uterine serosa. Due to the fact that the patient did have cyclic menstrual flow, her endometriosis may have arisen from retrograde menstruation or coelomic metaplasia induced by exogenous hormones.     

The effects of hormone replacement therapy on sleep-disordered breathing in postmenopausal women: a pilot study

STUDY OBJECTIVES: To evaluate the impact of estrogen and estrogen plus progesterone hormone-replacement therapy (HRT) on mild-to-moderate sleep-disordered breathing (SDB) in postmenopausal women. DESIGN AND SETTING: Within-subjects, progesterone placebo-controlled prospective HRT trial in a clinical laboratory. PARTICIPANTS: Six postmenopausal women, diagnosed with mild-moderate SDB. INTERVENTION: Transdermal estradiol and oral micronized progesterone. MEASUREMENTS AND RESULTS: Subjects underwent polysomnography (PSG) on four occasions: a screening/adaptation night; a baseline night on no HRT; and two nights on HRT: one night after 7 to 12 days on estrogen plus placebo followed by a second night after 7-13 days on estrogen plus progesterone. The PSG was performed with a Sandman computerized PSG system using a standard clinical montage. Modified sleep diaries were used in the baseline week and throughout the study period. Mood was measured with the 20-item version of the Positive and Negalive Affect Schedule (PANAS). Estrogen monotherapy was associated with a significant reduction in the overall apnea-hypopnea index (AHI) (from a mean of 22.7 events per hour at baseline to a mean of 12.2 events per hour), but the AHI reduction on estradiol plus progesterone relative to baseline was not statistically significant (AHI=16.2 events per hour). Similar results were found for the percentages of total sleep time and of total non-rapid eye movement sleep time with oxygen saturation less than 90%. Estrogen, neither alone nor in combination with progesterone, significantly altered PSG- or diary-based measures of total sleep time, time to sleep onset, or time awake after sleep onset. CONCLUSIONS: While the data are preliminary and based on a small number of subjects, estrogen appeared to have a substantial beneficial effect on measures of SDB in postmenopausal women. Overall, no additional benefit was seen with the addition of progesterone. In fact, progesterone attenuated the beneficial effects of estrogen in 4 out of the 6 participants.     

Initiation of GnRH antagonist on Day 1 of stimulation as compared to the long agonist protocol in PCOS patients. A randomized controlled trial: effect on hormonal levels and follicular development

BACKGROUND The optimal time for GnRH antagonist initiation is still debatable. The purpose of the current randomized controlled trial is to provide endocrine and follicular data during ovarian stimulation for IVF in patients with polycystic ovarian syndrome (PCOS) treated either with a long GnRH agonist scheme or a fixed day-1 GnRH antagonist protocol. METHODS Randomized patients in both groups (antagonist: n = 26; long agonist: n = 52) received oral contraceptive pill treatment for three weeks and a starting dose of 150 IU of follitropin beta. The primary outcome was E(2) level on Day 5 of stimulation, while secondary outcomes were follicular development, LH during ovarian stimulation and progesterone levels. RESULTS Significantly more follicles on days 5, 7 and 8 of stimulation, significantly higher estradiol (E(2)) levels on days 1, 3, 5, 7 and 8 and significantly higher progesterone levels on days 1, 5 and 8 of stimulation were observed in the antagonist when compared with the agonist group. E(2) was approximately twice as high in the antagonist when compared with the agonist group on day 5 of stimulation (432 versus 204 pg ml(-1), P lt; 0.001). These differences were accompanied by significantly lower LH levels on days 3 and 5 and significantly higher LH levels on days 1, 7 and 8 of stimulation in the antagonist when compared with the agonist group. CONCLUSIONS In PCOS patients undergoing IVF, initiation of GnRH antagonist concomitantly with recombinant FSH is associated with an earlier follicular growth and a different hormonal environment during the follicular phase when compared with the long agonist protocol.