Association between redundant endometrium and endometrial polyps: a pilot study.

BACKGROUND: The aim of this study was to explore the organic features of redundant endometrium (RE), we examined the expression of different endometrial hormone receptors, oncogenes, and cell replication markers, in normal endometrium (NE), endometrial polyps (EP) and RE specimens. METHODS: This was an experimental study examining endometrial tissue expression of estrogen receptors (ER1 and 2), progesterone receptors (PR-A+B), androgen receptor (AR), insulin receptor (Insulin-R), insulin-like growth factor receptor 1 (IGFR-1), thyroid hormone receptor (TH-RB), B-cell lymphoma 2 (Bcl-2), Ki67, HOXA10, in women with NE, EP and RE, of women undergoing hysteroscopy for benign gynecologic pathology. Specimens were separated in 3 groups: NE, EP, RE. Endometrial samples were processed for real-time RT-PCR analyses. Main outcome measure was tissue expression of the markers in the three groups. RESULTS: Of the 16 patients, 2 had NE, 8 had RE, 5 had EP, 1 had both, RE and EP. Compared to NE, RE and EP showed significantly increased Bcl-2, Insulin-R, ER-ß, PR-A+B, and TRB expression (P<0.044), with EP showing significantly increased PR-A+B, compared to RE (3.29±0.47 fg/µg RNA versus 1.86±0.34 fg/µg RNA; P=0.023). The other markers were not significantly different across the three groups: Ki67 appeared non-significantly decreased, while HOXA10, IGF-R1, AR, and ER-α, were non-significantly increased. CONCLUSIONS: RE showed biochemical characteristics different from NE. Similar to endometrial polyps, RE showed enhanced cell differentiation, but not cell replication. These changes in RE could be detrimental for embryo implantation and should be of consideration in women undergoing fertility treatments.

Endometrial Abnormalities: Correlation Between Different Diagnostic Modalities.

OBJECTIVES: We sought to evaluate the diagnostic accuracy of transvaginal ultrasound (TVUS) saline infusion sonohysterogram (SIS), and hysteroscopy for diagnosing endometrial abnormalities and their correlation with histological findings. In addition, we sought to validate the subsistence of a more subtle abnormality called "redundant endometrium" (RE). METHODS: Retrospective cohort study of patients presenting with infertility and diagnosed with endometrial abnormalities who underwent hysteroscopy and pathology evaluation. Each patient underwent TVUS at the first visit regardless of the cycle phase, followed by SIS during proliferative phase, and then hysteroscopy, which was performed when abnormal SIS findings were diagnosed. Endometrial abnormalities were categorized as polyps (EP), RE, or normal. Frequencies of the abnormalities were recorded for the 3 imaging modalities and their sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each. RESULTS: A total of 105 TVUS and 73 SIS were performed. Because of the frequent association of EP with RE, when all endometrial pathologies were combined, the three diagnostic modalities showed high sensitivity (TVUS 88.9%, SIS 100%, hysteroscopy 82.9%, respectively), but they also showed low specificity (TVUS 56.7%, SIS 56.1%, hysteroscopy 58.2%, respectively). Pathological evaluation showed isolated RE (26 cases), to harbor polyps (19.2%), disordered endometrium (19.2%), and complex atypical hyperplasia (3.8%). CONCLUSIONS: The three diagnostic modalities showed high sensitivity in diagnosing endometrial abnormalities. We identified RE as an independent endometrial abnormality. Benign endometrium is the predominant histology in RE, however, a small proportion harbors endometrial hyperplasia. Based on these results, we advocate further evaluation when this condition is diagnosed with TVUS, or SIS.

Options for preserving fertility in women undergoing gonadotoxic treatment.

Cancer chemotherapy and radiotherapy can be toxic to the ovaries, but women can improve their chances of preserving their fertility. Three options are available: gonadotropin-releasing hormone (GnRH) analogues, oocyte cryopreservation, and ovarian tissue cryopreservation. A fourth option, ovarian transposition, is valid for patients undergoing pelvic radiation but is not useful in patients undergoing chemotherapy.

Anti-Müllerian Hormone (AMH) regulates BRCA1 and BRCA2 gene expression after ovarian cortex transplantation.

OBJECTIVE: To test whether recombinant anti-Müllerian hormone (rAMH) could exert an inhibitory function on BRCA1/2 expression in human ovarian cortex. METHODS: Pilot study on ovariectomized nude mice xenotransplanted with human vitrified/warmed ovarian cortex and treated with rAMH via infusion pump. Twelve nude mice were ovariectomized and Alzet pumps delivering 1.23 mcg rAMH/day to reach a serum concentration of 17.5 ng/mL, or placebo (controls), were inserted intraabdominally. Previously vitrified/warmed 2x2 mm ovarian cortex fragments were transplanted on day 7 and then harvested on day 14 after pump placement. PCR analyses determined mRNA levels for BRCA1 and BRCA2 in the human ovarian cortex. RESULTS: In mice treated with rAMH, BRCA1 expression was significantly lower (0.196 fg/µg RNA, IQR 0.158, 0.236) than in controls (0.544 fg/µg RNA, IQR 0.458, 0.554; p = .030), while BRCA2 expression remained similar in rAMH mice (5.355 fg/µg RNA, IQR 4.479, 6.230) and in controls (4.011 fg/µg RNA, IQR 3.650, 4.182; p = .327). CONCLUSION: Administration of rAMH in the peri-transplant period caused downregulation of BRCA1, but not of BRCA2 expression, in human ovarian cortex. These results help our understanding of DNA repair mechanism in the ovarian cortex and identify AMH's possible protective effect on ovarian reserve in BRCA1 mutation carriers.

Fluid deficit calculation at hysteroscopy: could consideration of intraperitoneal fluid accumulation add insight to safety limits?

BACKGROUND: The current literature and guidelines are largely silent regarding the contribution of the fallopian tubes to the fluid deficit (FD) during hysteroscopy. We explored whether the FD could be in part due to transtubal passage. METHODS: This was a prospective cohort study. Patients who underwent hysteroscopy because of benign gynecologic pathology with, or without, laparoscopy were enrolled. The fluid deficit and, in laparoscopic cases, the amount of fluid found in the pelvis were prospectively reported. RESULTS: Comparisons between FD and intraperitoneal fluid were performed. Sixty-five patients were included in the study. Forty-five underwent hysteroscopy prior to laparoscopy and 20 patients underwent hysteroscopy-only. These were further divided into operative hysteroscopy and diagnostic hysteroscopy subgroups. In the laparoscopy group, the average FD was 525.9 mL (95% CI: 482.1-569.7) and the calculated FD due to intravasation was 286.6 mL (95%CI: 253.0-320.3). In the hysteroscopy without laparoscopy group, the average FD was 303.0 mL (95% CI: 85.2-520.8). There was no correlation between the intrauterine fluid pressure and the amount of FD, or the presence of intraperitoneal fluid. CONCLUSIONS: Most women with patent tubes undergoing hysteroscopy have accumulation of distention fluid in the pelvis and that the passage was not correlated with the intrauterine fluid pressure. These findings add new insight to the current guidelines, suggesting more accurate and patient-centered safety protocols.

Lack of Fetal Insulin Resistance in Maternal Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) affects 8-10% of women. NIH criteria for diagnosis include chronic anovulation and evidence of clinical or biochemical hyperandrogenism. PCOS is associated with adverse neonatal outcomes. Our hypothesis is that insulin resistance is increased in fetuses born to women with PCOS. This is a prospective cohort of women who delivered at our institution. Subjects with a body mass index < 20 or ≥ 50 kg/m2, multiple gestation, and major fetal malformations were excluded. Maternal blood was collected at admission, and umbilical cord blood was collected after delivery. Serum concentrations of insulin and glucose were measured from each sample. The homeostasis model assessment index of insulin resistance (HOMA-IR) was calculated (plasma glucose (mmol/L) × insulin (µU/mL)/22.5). The HOMA-IR from mothers and fetuses with PCOS was compared with mothers and fetuses without PCOS (controls). Mann-Whitney U test was utilized for statistical analysis. Forty-six women and fetal pairs were included; 28 with PCOS and 18 controls. Maternal insulin (20 [7.7-26.5] vs. 6.6 µU/ml [5.1-7.2]; p = 0.005) and HOMA-IR (3.9 [1.6-4.5] vs. 1.1 [0.9-1.3]; p = 0.01) were increased in the PCOS group. There was no statistical difference in fetal insulin, glucose, or HOMA-IR (p = 0.31) in the umbilical artery (p = 0.10; p = 0.34; p = 0.45, respectively) or the umbilical vein (p = 0.13; p = > 0.99; p = 0.31, respectively). Insulin resistance is present in non-diabetic pregnant women with PCOS, however not in their fetuses. This might explain variations in the occurrence of the adverse neonatal and maternal outcomes reported in PCOS.

Serum Anti-Müllerian hormone (AMH) in mothers with polycystic ovary syndrome (PCOS) and their term fetuses.

We sought to determine serum AMH levels in the maternal circulation, and the umbilical artery and vein, in normal women and women with PCOS, and their neonates at time of delivery. This represents a cross-sectional study of 57 pregnant patients who presented to the labor and delivery suite and subsequently delivered. We obtained maternal, as well as fetal blood from both, umbilical artery and vein. We measured serum concentrations of estradiol, AMH, testosterone and FSH. A total of 30 patients delivered a female and 27 a male neonate. Of them, 18/30 and 18/27 had a diagnosis of PCOS by NIH criteria. Mean age, BMI, weight gain in pregnancy, and gestational age did not differ between the two groups of mothers. AMH serum levels were statistically higher in women with PCOS (p < 0.005) and in their fetuses, independently of gender. Testosterone was higher in women with PCOS (p < 0.001), but there was no PCOS-related difference in their fetuses. FSH levels were significantly lower in PCOS than non-PCOS mothers carrying a male (p = 0.022), but not a female, fetus. AMH was positively correlated with maternal serum testosterone (p = 0.001) and negatively with fetal serum FSH (p < 0.026). In PCOS pregnancies, AMH was negatively correlated with maternal BMI (p = 0.019), menstrual cycle length (p = 0.035), and fetal uterine vein FSH (p = 0.021). In conclusion, at time of delivery, fetuses of women with PCOS had higher AMH levels and similar testosterone levels compared to fetuses from non-PCOS mothers, irrespective of gender. Our results may help explaining developmental differences in offspring of PCOS women.

Xenotransplantation of pre-pubertal ovarian cortex and prevention of follicle depletion with anti-Müllerian hormone (AMH).

OBJECTIVE: To determine whether recombinant AMH (rAMH) could prevent post-transplant follicular depletion by acting on the stemness markers Oct-4, Sox2, and NANOG. MATERIALS AND METHODS: This was an experimental study where 12 ovariectomized nude mice were xenotransplanted with vitrified/warmed ovarian cortex obtained from a pre-pubertal girl and Alzet pumps delivering rAMH, or placebo (control), were inserted intra-abdominally. Previously vitrified/warmed ovarian cortex fragments were transplanted after 7 days and then harvested after 14 days from pump placement. We performed real-time RT-PCR analyses, ELISA for AMH, FSH, and estradiol, histologic measurement of ovarian follicles, and immunohistochemistry for Ki67 and TUNEL. The main outcome measures were serum levels and tissue expression of the parameters under investigation and follicle count. RESULTS: Serum AMH, FSH, and estradiol reflected post-ovariectomy profiles and were mildly influenced by rAMH administration. Ovarian cortex expression of AMH, AMH-R2, VEGF, GDF9, Oct-4, and Sox2 was lower in rAMH mice than in controls, while NANOG was upregulated. There was a non-significant decrease in primordial follicles after vitrification-warming, and xenotransplantation further decreased this number. There were lower cell replication and depressed apoptosis in the rAMH group. CONCLUSIONS: Administration of recombinant AMH in the peri-transplant period did not protect the initial follicular depletion but decreased apoptosis and cellular activation and regulated stem cell markers' tissue expression. These results aid our understanding of the inhibitory effects of AMH on follicular development and show the benefit of administering exogenous AMH at the time of pre-pubertal ovarian cortex transplant to protect the follicles from pre-activation and premature depletion.

Relevance of Uterine Subseptations: What Length Should Warrant Hysteroscopic Resection?

OBJECTIVES: Existing recommendations warrant correction of uterine subseptations longer than 10 mm. We assessed whether a different subseptation length is indicated for intervention by evaluating the postoperative decrease in cavity width. METHODS: We conducted a prospective controlled cohort study at a university center. Healthy women and women with subseptations were evaluated with three-dimensional ultrasound before and after undergoing surgical resection of uterine subseptations by hysteroscopy. Measurement of the subseptum's length and width, and total cavity width, were obtained in both groups of women. We created a receiver operating characteristic curve using 7-mm cavity postoperative width change as the reference variable, and subseptation length as the outcome variable. Identifying a new subseptation length that warrants surgical intervention. RESULTS: Seventy-six women with subseptations and 77 with healthy uteri were included in the study. In the subseptate group, 50 had a subseptum less than 10 mm, and 26 were greater than 10 mm. Uterine and uterine cavity widths were significantly greater than in healthy women. The postoperative cavity width (28 ± 0.9 mm) was correlated with the preoperative subseptum length (R = 0.42; P = .016) and width (R = 0.54; P = .001) and was similar to healthy uteri. The receiver operator characteristic curve identified 5.9 mm (sensitivity = 100%, specificity = 41.4%) as a new threshold length of subseptation, which shows a postoperative cavity adjustment comparable to a subseptation greater than 10 mm. CONCLUSIONS: The relevance of subseptations shorter than 10 mm is currently undetermined and underestimated. Our data indicate a new subseptation cutoff length with postoperative remodeling and statistical relevance similar to longer subseptations. We propose a revision of the recommendations for surgical correction to include the objectively obtained subseptation length greater than or equal to 5.9 mm.

Fertility biomarkers to estimate metabolic risks in women with polycystic ovary syndrome.

PURPOSE: We sought to evaluate the relationship between the polycystic ovary syndrome (PCOS)-defining characteristics and the risk of developing metabolic complications in women presenting with complaints of infertility and/or menstrual irregularities and subsequently diagnosed with PCOS. METHODS: This was a cross-sectional study. Women presenting with complaints of infertility and/or irregular menses and diagnosed with PCOS by the Rotterdam criteria, underwent endocrine, metabolic, and ultrasound assessment in the early follicular phase. Reproductive and metabolic parameters were included in regression analysis models with the PCOS-defining characteristics; ROC curves were calculated for the significant predictors. RESULTS: Three hundred and seventy-four women with PCOS were included in our study. Oligo-anovulation, menstrual irregularities, and hirsutism were not predictive of any of the variables. Ovarian volume, follicle count, and biochemical hyperandrogenism were predictors for hormonal, metabolic, and endometrial complications. The relationships were independent of age and body mass index. ROC curves identified lower cut-off values of the PCOS-defining characteristics to predict patients' risks of hyperinsulinemia, dyslipidemia, and glucose intolerance. CONCLUSIONS: Adverse metabolic effects of PCOS are already present in women at the time they present complaining of infertility and/or irregular menses. Hyperandrogenism and ultrasound can assist in predicting the patients' concomitant metabolic abnormalities and can aid physicians in tailoring counseling for effective preventive strategies.

Goserelin fosters bone elongation but does not prevent ovarian damage in cyclophosphamide-treated prepubertal mice.

OBJECTIVE: To evaluate whether administration of goserelin, a gonadotropin-releasing hormone (GnRH) agonist, could prevent acute or chronic ovarian insufficiency from cyclophosphamide (CTX) administration to prepubertal mice. DESIGN: Animal study. SETTING: University center. ANIMAL(S): C57BL/6J mouse strain. INTERVENTION(S): Goserelin administered on day 13 of life, CTX on day 18 of life, euthanasia on day 20 (prepubertal), 56 (pubertal), or 92 of life (mature), measurements of body weight, length, uterine weight, serum antimüllerian hormone and follicle-stimulating hormone, and histologic assessment of ovarian follicles and femur growth, and apoptotic rates by TUNEL. MAIN OUTCOME MEASURE(S): Assessment of prevention of ovarian insufficiency and defective bone elongation from CTX administration. RESULT(S): Prepubertal mice were randomly assigned to three groups: control (G1), CTX (G2), and goserelin + CTX (GG). A total of 63 mice were euthanized in the three groups. Body weight and length, and uterine weight did not differ among groups at any age. Ovarian size was not different in the three groups. There were fewer primordial and primary follicles/mm(2) in groups GG and G2 than in group G1 at all ages, but there was no difference between groups GG and G2. Corpora lutea/mm(2) were decreased in group GG versus G2. Femur length was statistically significantly greater in groups G1 and GG than group G2. CONCLUSION(S): Goserelin administered to prepubertal mice during CTX treatment fosters maintenance of bone elongation but does not protect the ovaries from follicular depletion.

Robot assisted laparoscopic documentation of endometriosis.

The increased confirmation of endometriosis noted using robotically assisted laparoscopy may be the result of multiple factors, including the three-dimensional view provided with the robot, increased attention and awareness while using new technology, increased time spent considering histologic documentation in preparation for publication, or general improvement with experience.

Serum markers of ovarian reserve and ovarian histology in adult mice treated with cyclophosphamide in pre-pubertal age.

PURPOSE: AMH is used to quantify the extent of follicular pool in postpubertal women, but its value after chemotherapy is unclear. We tested AMH as a marker of follicular reserve in adult mice treated with cyclophosphamide (CTX) in prepubertal age. METHODS: Mice received placebo or CTX at age 18 days. AMH and FSH were assessed on day 43, 56, and 95 of life. Ovaries were fixed in formalin, embedded in paraffin, and stained with H&E and TUNEL. Follicular apoptosis was graded. RESULTS: All mice exposed to CTX had a decreased number of follicles/mm(2) and significantly decreased AMH, but only 48 % of pubertal and 81 % of adult mice had increased FSH. Over time, there was an increase in FSH (p < 0.05), but not a concurrent decrease in AMH, while in controls, FSH remained stable and AMH decreased. There was no correlation between histological and serological markers. CONCLUSIONS: CTX administration to pre-pubertal mice caused various degrees of residual function, which were reflected by FSH, but not by AMH or by the number of ovarian follicles. AMH served as a marker of quantitative, and FSH of qualitative, residual ovarian function.

Endometrial signaling pathways during ovarian stimulation for assisted reproduction technology.

OBJECTIVE: To determine the effects of different hormonal levels on endometrial biochemical development during ovulation induction for assisted reproduction technology (ART) cycles. DESIGN: Prospective controlled study. SETTING: University center. PATIENT(S): Nine women during a natural cycle (control) and 9 oocyte donors (treated) during an ART cycle. INTERVENTION(S): At the time consistent with day 3 embryo transfer (LH+5 in control, hCG+5 in treated), transvaginal ultrasound, endometrial biopsy, and blood sampling were performed. Real-time reverse-transcription polymerase chain reaction was used to measure mRNA levels for insulin receptor (InsR), type I IGF receptor (IGFRI), prolactin receptor (PRL-R), androgen receptor (AR), TSH receptor (TSHR), nuclear receptors for T3 and T4 (TRα1, TRα2, and TRß1), iodothyronine deiodinase (DIO2), and 1,25-dihydroxyvitamin D3 receptor (VDR) in the endometrial tissue. MAIN OUTCOME MEASURE(S): Biochemical endometrial development. RESULT(S): IGFRI mRNA levels were 69% lower in treated patients than in control subjects, 0.12 ± 0.005 pg/µg RNA versus 0.39 ± 0.01 pg/µg RNA. TSHR mRNA was 57% lower, 2.6 ± 0.1 fg/µg RNA versus 6.0 ± 0.2 fg/µg RNA. TRα1 and TRα2 mRNA did not change, but TRß1 mRNA levels were 63% higher. DIO2 mRNA was 63% lower, 1.2 ± 0.07 pg/µg RNA versus 3.2 ± 0.2 pg/µg RNA. InsR mRNA levels, despite being 68% lower in treated patients, did not reach significance, and PRL-R, AR, and VDR did not significantly change. CONCLUSION(S): Exposure of the endometrium to ovarian stimulation appears to influence insulin and thyroid hormone signaling pathways in the decidua at day 3 embryo transfer, whereas prolactin, androgen, and vitamin D pathways are uninfluenced. These findings echo the known delayed endometrial maturation during ovarian stimulation.

GnRH-analogues for ovarian protection in childhood cancer patients: how adult hypotheses are relevant in prepubertal females.

Systemic chemotherapy frequently causes primary ovarian insufficiency. In prepubertal girls, currently the only option to preserve ovarian function is ovarian tissue preservation. The use of gonadotropin-releasing hormone analogues given in combination with chemotherapy has been studied in reproductive age women. The exact mechanism is unknown, but some of the proposed protective mechanisms could theoretically protect the prepubertal ovary as it has been theorized in many of the studies on reproductive age women. None of the studies implies an adverse affect of GnRH analogue administration in terms of worsening health or cancer status. As 83% of children diagnosed with cancer will survive into adulthood, GnRH analogue administration to female childhood cancer patients in combination with chemotherapy might represent a valuable attempt to preserve future ovarian function and fertility when ovarian tissue preservation is not an option.

Somatic and reproductive outcomes in mice treated with cyclophosphamide in pre-pubertal age.

Disruption in the normal timing of female puberty, such as in pre-pubertal cancer treatments, can cause abnormal somatic development. We sought to evaluate the impact of cyclophosphamide (CTX) on the somatic, uterine, and ovarian, development of pre-pubertal mice. Pre-pubertal (day 18 of life) C57BL/6J female mice were randomized to receive placebo (group 1A and 1B), 200 mg/kg CTX (group 2A), or 120 mg/kg CTX (group 2B). Mice were euthanized on day 56 (A groups) or 95 (B groups) of life. Body weight and length, uterine and ovarian weight and right femur length and weight were measured, and ovarian insufficiency was assessed. Data were analyzed using ANOVA and t-test. Body weight and length did not differ among groups at time of euthanasia. The femur was shorter and weighed less in mice treated with CTX than in controls. Uterine weight was lower in group 2B than 1B (46.1 mg, 95% CI: 42.9-49.4, vs. 62.2 mg, 95% CI: 58.5-65.8, respectively; p = 0.005) and was lower in mice that developed ovarian insufficiency than in mice that did not (p < 0.05). Ovarian weight was lower in mice treated with CTX, regardless of whether they developed ovarian insufficiency. Even with no observable effect on adult body length and weight, CTX treatment in pre-pubertal mice appears to negatively affect femur, uterine, and ovarian development. However, uterine development seems to be dependent on the hormonal status created by CTX more than on its direct effect.

Applicability of adult techniques for ovarian preservation to childhood cancer patients.

PURPOSE: To appraise the feasibility of current adult medical and surgical techniques for ovarian preservation in pre-pubertal and adolescent girls with cancer. METHODS: Literature search using PubMed and SCOPUS up to February 2012. In addition, the reference lists of selected studies and all identified systematic and narrative reviews were scanned for relevant references. Inclusion criteria were ovarian preservation and cancer. Exclusion criteria were non-English publications, letters, personal communications, and ovarian preservation for conditions other than cancer. RESULTS: Data from the selected publications was interpreted and discussed in the relevant sections. Cryopreservation of ovarian tissue followed by autologous transplant represents the only surgical option available for pre-pubertal girls and adolescents who cannot delay the start of chemotherapy. Few studies report on pre-pubertal and adolescent girls undergoing ovarian preservation surgeries with good harvesting, and no follow-up has been conveyed, to date. Outcomes of ovarian function after ovarian suppression with GnRH-analogs in adults have been controversial and no reports are available for pre-pubertal girls. CONCLUSIONS: Autologous transplantation of cryopreserved ovarian cortex probably represents the best option for preservation of fertility and hormonal function in childhood cancer females; however, future research needs to address the safety of this technique, especially in patients with blood-borne cancers. Ovarian suppression with GnRH-analogs at the time of chemotherapy treatment has not proven to be superior to non-suppression for fertility preservation purposes in adults. Not enough evidence is presently available in childhood cancer patients.

Fetal reduction for hyperreactio luteinalis.

OBJECTIVE: To present an unusual case of hyperreactio luteinalis and a comprehensive review of the recent literature. Hyperreactio luteinalis is a benign ovarian condition of pregnancy that at times becomes life threatening. The medical literature provides only case reports. DESIGN: Case report and systematic review of the literature. SETTING: University Center. PATIENT(S): A multiparous woman with polycystic ovary syndrome who underwent ovarian stimulation with oral and injectable medications and conceived triplets. She presented at 10 weeks of pregnancy with hyperreactio luteinalis. INTERVENTION(S): Fetal reduction to singleton. MAIN OUTCOME MEASURE(S): Resolution of condition. RESULT(S): The condition resolved 6 weeks after fetal reduction. The patient delivered at term without further complications. CONCLUSION(S): Our review showed that many unnecessary surgeries are performed to treat hyperreactio luteinalis. When feasible, fetal reduction may improve outcome and represents an effective approach that does not compromise maternal well-being or future fertility.

Endometrial morphology and modulation of hormone receptors during ovarian stimulation for assisted reproductive technology cycles.

OBJECTIVE: To study the biochemical and morphologic implications of different hormonal levels on endometrial development during assisted reproductive technology (ART) cycles. DESIGN: Prospective, controlled study. SETTING: University center. PATIENT(S): Eleven women during a natural cycle (controls) and 11 oocyte donors during an ART cycle (treated). INTERVENTION(S): At the time consistent with day-3 ET, a transvaginal ultrasound, an endometrial biopsy, and blood sampling were performed. Morphology and thickness of the endometrial stripe were recorded. Real-time reverse transcriptase-polymerase chain reaction was used to measure messenger RNA (mRNA) levels for estrogen receptor (ER)-α, ER-ß, P receptor (PR)-A, and PR-B in the endometrial tissue. MAIN OUTCOME MEASURE(S): To evaluate morphologic and biochemical endometrial development. RESULT(S): Endometrium was mostly trilaminar (proliferative-like pattern) and thicker in the treated group, as opposed to homogeneous and thinner in the controls. The PR-B mRNA expression increased 41% in treated patients; PR-A mRNA expression, instead, was unchanged. Serum E(2) and P were higher in the treated group than in controls. In contrast, FSH and LH levels were lower in the treated group. CONCLUSION(S): When compared with natural cycles, exposure of the endometrium to high hormone levels during ovarian stimulation significantly increased PR-B receptor expression at the time of ET. Concurrently, a proliferative-like endometrial pattern persisted. These findings reflect a delayed endometrial development in ART.

Endometrial thickness dynamics and morphologic characteristics during pituitary downregulation with antagonists in assisted reproductive technology cycles.

OBJECTIVE: The purpose of this study was to evaluate whether the dynamics of endometrial stripe thickness during gonadotropin-releasing hormone (GnRH) antagonist pituitary downregulation in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles are related to implantation and pregnancy outcomes. METHODS: This retrospective cohort study evaluated 115 conventional IVF/ICSI cycles. All patients underwent ovarian stimulation with gonadotropins and the GnRH antagonist ganirelix acetate. The endometrial stripe was measured transvaginally daily from the day of initial GnRH antagonist administration to the day of the human chorionic gonadotropin (hCG) trigger and then transabdominally on the day of embryo transfer. We created 5 categories (0-4) of endometrial thickness variation, considering significant a daily variation of 1.5 mm. Our aim was to predict whether the endometrial thickness dynamics or morphologic characteristics were related to the duration of ovarian stimulation, duration of ganirelix use, or estradiol levels during ovarian stimulation and whether they would influence implantation and pregnancy rates. RESULTS: No relationship was found between the duration of ovarian stimulation, duration of ganirelix use, and estradiol level (expressed as the area under the curve), and endometrial thickness dynamics or morphologic characteristics. Despite a thinner endometrial thickness in 37% of the cycles on the day of the hCG trigger compared with the beginning of GnRH antagonist stimulation, there was no correlation between endometrial dynamics and pregnancy outcomes. There was, instead, a positive relationship between a trilaminar endometrial morphologic pattern with a positive pregnancy test result, successful implantation, and ongoing pregnancy (P < .05). CONCLUSIONS: Despite a net decrease in thickness in almost 50% of cases, endometrial dynamics did not correlate with pregnancy outcomes. Conversely, a trilaminar endometrial morphologic pattern on the day of embryo transfer was positively related to pregnancy outcomes.