IVF outcomes of embryos with abnormal PGT-A biopsy previously refused transfer: a prospective cohort study.

STUDY QUESTION: What are the outcomes for patients who choose to move embryos diagnosed as abnormal by preimplantation genetic testing for aneuploidy (PGT-A) to a new institution for transfer after the diagnosing institution refused to transfer them? SUMMARY ANSWER: Many patients seek to have selected embryos with PGT-A abnormal trophectoderm biopsies transferred recognizing that these embryos can still offer a chance of pregnancy and live birth. WHAT IS KNOWN ALREADY: : PGT-A is a widely practiced method of selecting embryos for transfer based on biopsy of a few cells. Many clinical practices refuse to transfer PGT-A abnormal embryos even when there are no other 'normal' embryos available. STUDY DESIGN, SIZE, DURATION: This is a prospective cohort of 69 couples who, since 2014, moved a total of 444 PGT-A abnormal embryos previously refused transfer at their parent institutions to our practice. Among these, 50 patients have, thus far, undergone 57 transfer cycles of 141 embryos. PARTICIPANTS/MATERIALS, SETTING, METHODS: Embryos diagnosed at other institutions by PGT-A as abnormal (mostly using next generation sequencing) were moved to our academically affiliated private fertility and research center in New York City. Female age at retrieval was 41.35 ± 3.98 years, 74% were Caucasian, 12% Asian and 10% were of African descent. All embryos identified as PGT-A abnormal among prospectively identified couples were recorded in our center's registry. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 144 embryos transferred 102 (72.3%) had only 1 or 2 chromosomal abnormalities, 30 (21.3%) had 3 or more and 9 (6.4%) were 'undiagnosed' because of degraded DNA, yet still had been refused transfer. Transfer of PGT-A abnormal embryos resulted in 8 live births, 11 miscarriages and no voluntary terminations. One child was born with a segmental duplication and required repair of coarctation of the aorta as a newborn. Many couples with only PGT-A abnormal embryos are willing to have their PGT-A abnormal embryos transferred and such transfers can result in the establishment of ongoing euploid pregnancies and live births. LIMITATIONS, REASONS FOR CAUTION: Findings in this case series represent couples who chose to have their embryos transferred after having been refused transfer elsewhere and may not be representative of the wider population of couples undergoing IVF with PGT-A in general. Not all abnormal phenotypes present in the immediate postnatal period so it will be important to continue to follow the development of these children. WIDER IMPLICATIONS OF THE FINDINGS: PGT-A can result in a clinics refusal to transfer embryos with abnormal PGT-A biopsies, even those with mosaic findings, consequently large numbers of infertile women are prematurely advised that their only chance of motherhood is through third-party egg-donation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by intramural funds from the Center for Human Reproduction and the not-for-profit research Foundation for Reproductive Medicine, both in New York, NY, USA. N.G. and D.H.B. are listed as co-inventors on several U.S. patents. One of these patents (US Patent# 7,615,544) relates to pre-supplementation of hypo-androgenic infertile women with androgens, such as DHEA and testosterone and, therefore, at least peripherally related to the subject of this manuscript. N.G. and D.F.A. also received travel funds and speaker honoraria from several pharmaceutical and medical device companies, though none related to the here presented subject and manuscript. N.G. is a shareholder in Fertility Nutraceuticals and he and D.H.B. receive royalty payments from Fertility Nutraceuticals LLC. TRIAL REGISTRATION NUMBER: N/A.

Age, body weight and ovarian function affect oocyte size and morphology in non-PCOS patients undergoing intracytoplasmic sperm injection (ICSI).

The size of oocytes was previously reported to be smaller in obese women with polycystic ovary syndrome (PCOS). In the present prospective cohort study, we sought to determine whether oocyte size and morphology are associated with patient characteristics in non-PCOS women. Oocyte and oolemmal diameter were measured, enlarged perivitelline space (PVS) and ooplasmic granulation were assessed in 308 MII oocytes from 77 IVF/ICSI couples. Statistical analysis was undertaken using SAS version 9.4 (SAS institute Inc., USA). Continuous values are presented as mean ± SD and compared using a two-sample t-test or Mann-Whitney U test as appropriate. Categorical parameters are presented as proportions and compared using a Fisher exact test. Logistic and linear regression models were used to control for the effect of age for categorical and continuous variables respectively. P-value < 0.05 was considered statistically significant. Patients presented with a mean age of 40.3±5.0 years, had a BMI of 25.1±6.1 kg/m2, median AMH levels of 0.6 ng/ml and produced a median of 4 oocytes. Mean total oocyte diameter was 163.2±7.4 µm (range 145.8-182.1 µm), while oolemmal diameter was 109.4±4.1 µm (range 98.5-122.3 µm). After adjusting for age and ovarian reserve increasing BMI was associated with decreased total oocyte diameter (p<0.05). Total oocyte diameter was also inversely associated with AMH levels (p = 0.03) and oocyte yield (p = 0.04). In contrast to total oocyte diameter, oolemmal diameter was not related to patient characteristics. Younger women and those with large oocyte yields demonstrated fewer oocytes with ooplasmic granulation (p<0.05 and p = 0.01). After adjustments for age, ooplasmic granulation was also less frequently observed in oocytes from women with higher AMH (p = 0.03) and increasing BMI (p<0.01). Fertilization was more likely in oocytes with larger oolemmal diameter (p = 0.008). Embryos from oocytes with larger total and ooplasmic diameters were more likely to be transferred or frozen (p = 0.004 and p = 0.01). In non-PCOS infertile women, BMI and ovarian function relate to total oocyte diameter. These results expand on previously observed associations between oocyte size and BMI in women with PCOS. They indicate the importance of detailed oocyte assessments, which may aid the currently used criteria for embryo selection and help to better understand how oocyte status is associated with later embryo development.

A pilot cohort study of granulocyte colony-stimulating factor in the treatment of unresponsive thin endometrium resistant to standard therapies.

STUDY QUESTION: Is thin endometrium unresponsive to standard treatments expandable by intrauterine perfusion with granulocyte colony-stimulating factor (G-CSF)? SUMMARY ANSWER: This cohort study is supportive of the effectiveness of G-CSF in expanding chronically unresponsive endometria. WHAT IS KNOWN ALREADY: In a previous small case series, we reported the successful off-label use of G-CSF in four consecutive patients, who had previously failed to expand their endometria beyond 6.9 mm with the use of standard treatments. STUDY DESIGN, SIZE AND DURATION: In a prospective observational cohort pilot study over 18 months, we described 21 consecutive infertile women with endometria <7 mm on the day of hCG administration in their first IVF cycles at our center. All previous cycles using traditional treatments with estradiol, sildenafil citrate (Viagra™) and/or beta-blockers had been unsuccessful. G-CSF (Nupogen™) was administered per intrauterine catheter by slow infusion before noon on the day of hCG administration. If the endometrium had not reached at least a 7-mm within 48h, a second infusion was given following oocyte retrieval. Primary and secondary main outcomes were an increase in endometrial thickness and clinical pregnancy, respectively. Endometrial thickness was assessed by vaginal ultrasound at the most expanded area of the endometrial stripe. PARTICIPANTS/MATERIALS, SETTINGS AND METHOD: This study was uncontrolled, each patient serving as her own control in a prospective evaluation of endometrial thickness. The mean ± SD age of the cohort was 40.5 ± 6.6 years, gravidity was 1.8 ± 2.1 (range 0-7) and parity was 0.4 ± 1.1 (range 0-4); 76.2% of women had, based on age-specific FSH and anti-Müllerian hormone, an objective diagnosis of diminished ovarian reserve and had failed 2.0 ± 2.1 prior IVF cycles elsewhere. MAIN RESULTS AND THE ROLE OF CHANCE: With 5.2 ± 1.9 days between G-CSF perfusions and embryo transfers, endometrial thickness increased from 6.4 ± 1.4 to 9.3 ± 2.1 mm (P < 0.001). The Δ in change was 2.9 ± 2.0 mm, and did not vary between conception and non-conception cycles. A 19.1% ongoing clinical pregnancy rate was observed, excluding one ectopic pregnancy. LIMITATIONS AND REASONS FOR CAUTION: Small sample size (but a highly selected patient population) in an uncontrolled cohort study and in unselected first IVF cycles at our center. WIDER IMPLICATIONS OF THE FINDINGS: This pilot study supports the utility of G-CSF in the treatment of chronically thin endometrium and suggests that such treatment will, in very adversely affected patients, result in low but very reasonable clinical pregnancy rates. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Foundation for Reproductive Medicine, New York, New York, USA, a not-for-profit research foundation and intramural grants from the Center for Human Reproduction (CHR)-New York. N.G. and D.H.B. are members of the board of the Foundation for Reproductive Medicine. N.G. is owner of CHR-New York, where the study was conducted. N.G. and D.H.B. have been recipients of research awards, travel grants and speaker honoraria from various pharmaceutical and medical device companies. None of these companies was, however, in any way associated with the materials and the manuscript presented here. N.G. and D.H.B. are listed as co-inventors on a number of awarded and still pending U.S. patents, none related to the materials presented here. N.G. is on the board of a medically related company, not in any way associated with the data presented here.

Reducing the risk of high-order multiple pregnancy after ovarian stimulation with gonadotropins.

BACKGROUND: The incidence of multiple gestation after therapy for infertility is especially high among women in whom ovulation is induced with gonadotropins. Whether the number of high-order multiple pregnancies (those with three or more fetuses) can be reduced is not known. METHODS: We analyzed data on 3347 consecutive treatment cycles in 1494 infertile women, 441 of which resulted in pregnancy. The data collected included the peak serum estradiol concentration, the number of follicles 16 mm or larger in diameter, and the total number of follicles on the day of induction of ovulation with human chorionic gonadotropin. Receiver-operating-characteristic curves and ordinal logistic-regression analyses were used to identify values that predicted multiple conceptions. RESULTS: Among the 441 pregnancies, 314 resulted from the conception of singletons, 88 of twins, 22 of triplets, 10 of quadruplets, 5 of quintuplets, and 2 of sextuplets. Neither the number of follicles 16 mm or larger nor peak serum estradiol concentrations greater than 2000 or 2500 pg per milliliter (7342 or 9178 pmol per liter) (the cutoff values currently in wide use) were significantly associated with the incidence of high-order multiple pregnancy. However, increasing total numbers of follicles and increasing peak serum estradiol concentrations correlated significantly with an increasing risk of high-order multiple pregnancy (P<0.001), as did younger age (P=0.008). The risk of high-order multiple pregnancy was significantly increased in women with a peak serum estradiol concentration of 1385 pg per milliliter (5084 pmol per liter) or higher (multivariate odds ratio, 1.9; 95 percent confidence interval, 1.3 to 2.8) or with seven or more follicles (multivariate odds ratio, 2.1; 95 percent confidence interval, 1.2 to 3.9) on the day of induction of ovulation. CONCLUSIONS: Gonadotropin stimulation that is less intensive than is currently customary may reduce the incidence of high-order multiple pregnancy in infertile women, though only to a limited extent and at the expense of overall pregnancy rates.

Estradiol/progesterone substitution in the luteal phase improves pregnancy rates in stimulated cycles--but only in younger women.

Innumerable studies have attempted to demonstrate that hormonal support of the luteal phase during ovulation induction cycles improves pregnancy rates. None has, however, so far been able to confirm the validity of such treatment conclusively, possibly because most studies only utilized progesterone substitution. Since luteal phase endometrium also requires estradiol support, this study attempted to investigate whether hormone substitution with progesterone and estradiol would be more successful in improving pregnancy rates. Amongst approximately 7500 consecutive ovulation induction cycles were identified prospectively which were characterized by a precipitous drop of luteal phase serum estradiol levels by more than 50% over a 48 hour period within 10 days from hCG administration. Those cycles were prospectively randomized to oral micronized estradiol substitution (Group I) or not (Group II), while both groups received routine progesterone substitution of the luteal phase. Cycles were then evaluated in regards to the occurrence of chemical, ectopic and clinical pregnancies. One hundred sixty-three Group I cycles resulted in 34 pregnancies (20.9%), which compared favorably to 21 pregnancies in 167 Group II patients (12.6%) (x2[1] = 4.06; p < 0.04). The advantage for Group I cycles (29/95 pregnancies, 31%) vs. Group II cycles (16/105, 15%) became even more pronounced when only women up to age 35 years were evaluated. Estradiol substitution maintained a significant advantage until age 38 (x2 [1] = 6.87; p < 0.009). While gravidity did not affect pregnancy success, estradiol substitution in Group I benefited nulliparous (23% pregnancy rate) over multiparous women (12% pregnancy rate) (x2 [2] = 6.86; p< 0.03). This association was, however, age-dependent. A combined estradiol and progesterone substitution of the luteal phase of ovulation induction cycles increases the overall pregnancy rate. Since estradiol substitution was initiated in this study only once a precipitous drop in serum estradiol levels had already taken place, an even larger improvement in pregnancy rates could conceivably be possible if earlier estradiol substitution of the luteal phase is initiated. A further expansion of investigations of similar protocols for routine ovulation induction and in vitro fertilization (IVF) cycles may be indicated, especially in women below age 38 years and in nulliparous females.

Resection of uterine septum using gynaecoradiological techniques.

This paper presents further refinements in our technique for the resection of uterine septum. Fourteen patients [infertility (n = 9) and recurrent miscarriages (n = 5)] underwent in-office resection of a uterine septum under fluoroscopic control. The main outcome measure was complete resection of uterine septum. Resections were carried out using either hysteroscopic scissors in combination with a specially designed uterine balloon catheter, or microlaparoscopy scissors in conjunction with a cervical cannula. In all patients the septum was successfully resected without any intra-operative complications. We conclude that ambulatory gynaecoradiological resection of uterine septa is a safe and simple procedure. It avoids utilization of expensive operating room time, general anaesthesia, and some complications associated with hysteroscopic resection, such as fluid retention and electrolyte imbalance.

Octreotide is not useful for clomiphene citrate resistance in patients with polycystic ovary syndrome but may reduce the likelihood of ovarian hyperstimulation syndrome.

OBJECTIVE: To determine whether octreotide is effective for ovulation induction in patients with polycystic ovary syndrome (PCOS) and clomiphene citrate resistance or for reduction of the risk of ovarian hyperstimulation syndrome (OHSS) with gonadotropin therapy. DESIGN: Prospective, double-blind, placebo-controlled, crossover trial. SETTING: Private infertility practice. PATIENT(S): Twelve patients with PCOS undergoing therapy for infertility. INTERVENTION(S): The patients were assigned randomly to receive either octreotide or placebo. Those with clomiphene citrate-resistant PCOS received clomiphene citrate, 150 mg. Patients at risk for the development of OHSS received urinary FSH for ovulation induction. MAIN OUTCOME MEASURE(S): Ovulation, pregnancy, the development of OHSS, and levels of fasting insulin, insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, testosterone, androstenedione, DHEAS, E2, LH, and FSH. RESULT(S): Octreotide significantly reduced levels of fasting insulin, insulin-like growth factor 1, and LH in both clomiphene citrate- and urinary FSH-stimulated cycles. Levels of insulin-like growth factor binding protein 3 were increased. Two of six clomiphene citrate-stimulated cycles reached ovulation with the use of either octreotide or placebo. In urinary FSH-stimulated cycles, patients who received octreotide had significantly lower E2 levels at the time of hCG administration and fewer mature follicles. No cases of OHSS occurred in either group. One pregnancy occurred in each group. CONCLUSION(S): Octreotide was no more effective than placebo for clomiphene citrate resistance in patients with PCOS, but it did reduce E2 levels and follicle numbers when combined with urinary FSH. Thus, octreotide may reduce the incidence of OHSS in patients with PCOS.

Lysis of intrauterine adhesions using gynecoradiologic techniques.

OBJECTIVE: To present further experience with in-office lysis of intrauterine adhesions under fluoroscopic control using a specially designed catheter. DESIGN: Prospective study. SETTING: Medical school-affiliated infertility center. PATIENT(S): Seventeen infertile patients undergoing routine gynecoradiologic investigation as part of an initial infertility workup. INTERVENTION(S): The initial hysterosalpinography was performed with a commercially available uterine catheter that seals off the uterine cavity before injection of contrast. If intrauterine adhesions were diagnosed, an immediate attempt at lysis was made using the catheter's balloon tip or hysteroscopic scissors, which were inserted through the main port of the catheter. The procedures were carried out using a paracervical block or IV analgesia. MAIN OUTCOME MEASURE(S): Normal uterine cavity after lysis of intrauterine adhesions. RESULT(S): Seventeen patients underwent lysis of intrauterine adhesions. In 13 patients (9 mild, 3 moderate, and 1 severe), the adhesions were lysed successfully (81.2%). Among those, nine procedures were performed with the balloon and four with scissors. In 4 cases (2 moderate and 2 severe), lysis of adhesions was only partially successful. These procedures had to be abandoned prematurely because of patient discomfort before attempting the use of scissors (n = 1), extravasation of dye into the myometrium making visualization difficult (n = 1), and thick, fibrotic adhesions that were resistant to scissors (n = 2). CONCLUSION(S): In-office lysis of intrauterine adhesions under gynecoradiologic control can be carried out safely in the majority of patients, using minimally invasive techniques. The potential cost savings in comparison with endoscopic procedures, which require utilization of expensive operating room time, are especially relevant in today's cost-conscious managed care environment. Only failures of in-office procedures would reach the operating room under the algorithm proposed here.

Limited success using the "flare" protocol in poor responders in cycles with low basal follicle-stimulating hormone levels during in vitro fertilization.

OBJECTIVE: To assess an alternate protocol for stimulating poor responders. DESIGN: Prospective clinical study. SETTING: University-affiliated infertility clinic. PATIENT(S): Eighty poor responders. INTERVENTION(S): Stimulation was withheld until patients fulfilled the following criteria: basal FSH < or = 12 mIU/mL (conversion factor to SI unit, 1.00) with concurrent E2 level < or = 100 pg/mL (conversion factor to SI unit, 3.671), and P level < or = 1.0 ng/mL (conversion factor to SI unit, 3.467). They then started leuprolide acetate on cycle day 2 and a high dose of gonadotropins on cycle day 3. MAIN OUTCOME MEASURE(S): Stimulation response and pregnancy rates (PRs). RESULT(S): Nineteen cycles (23.8%) were canceled because of poor ovarian response. The mean E2 level on day of hCG was 2,578 +/- 1,339 pg/mL (9,464 +/- 4,915 pmol/L) (range, 789 to 5934 pg/mL [2,896 to 21,784 pmol/L]). The number of oocytes retrieved was 10 +/- 6.6 (range, 1 to 37). Nine patients did not have ET (failed fertilization [n = 5], no cleavage of preembryos [n = 3], freeze all [n = 1]). The number of pre-embryos transferred was 3.9 +/- 1.6 (range, 1 to 8). The clinical pregnancy rate was 7 of 61 (11.5%) per retrieval, and 7 of 52 (13.4%) per transfer with an implantation rate of 7 of 201 (3.5%). Three patients miscarried with an ongoing PR of 4 of 61 (6.5%) per retrieval and 4 of 52 (7.6%) per transfer. CONCLUSION(S): Poor responders undergoing controlled ovarian hyperstimulation with the "flare" protocol in cycles with low basal FSH will often show adequate ovarian response and reach oocyte retrieval and ET. The PRs, however, remain low.

What is the radiation exposure to patients during a gynecoradiologic procedure?

OBJECTIVE: To evaluate the risk of radiation exposure to infertility patients during a gynecoradiologic procedure. DESIGN: Retrospective clinical study. SETTING: Medical school-affiliated infertility center. PATIENT(S): Three hundred thirty-two consecutive infertility patients undergoing a gynecoradiologic procedure. INTERVENTION(S): Patients underwent a gynecoradiologic procedure as part of their infertility workup and the fluoroscopic exposure time was analyzed. MAIN OUTCOME MEASURE(S): The fluoroscopic exposure (rad time) during gynecoradiologic procedures, including hysterosalpingogram (HSG), selective salpingography, tubal catheterization, and others. RESULT(S): The rad time (mean +/- SD) was 63 +/- 54 seconds for normal HSG (n = 94, range 17 to 404 seconds), 100 +/- 61 seconds for abnormal HSG (n = 53, range 28 to 272 seconds), 111 +/- 57 seconds for unilateral selective salpingography (n = 36, range 31 to 324 seconds), 142 +/- 74 seconds for bilateral selective salpingography (n = 87, range 40 to 430 seconds), 176 +/- 77 seconds for unilateral tubal catheterization (n = 27, range 70 to 342 seconds), and 239 +/- 82 seconds for bilateral tubal catheterization (n = 30, range 110 to 381 seconds). Five patients had other procedures, such as lysis of intrauterine adhesions (n = 2) and resection of an uterine septum (n = 3), for which the rad time was in a range of 180 to 300 seconds. CONCLUSION(S): The radiation exposure of patients during a gynecoradiologic procedure, using previously described standard techniques, is well within established margins of safety.

Elevated tubal perfusion pressures during selective salpingography are highly suggestive of tubal endometriosis.

OBJECTIVE: To investigate the possible etiologies of elevated tubal perfusion pressures. DESIGN: Analysis of 48 consecutive female patients with infertility who underwent laparoscopy and a gynecoradiological investigation as part of their infertility work-up. SETTING: Academically affiliated infertility center. INTERVENTIONS: A gynecoradiological investigation was performed using a previously reported standardized contrast injection system. Laparoscopy was performed routinely. RESULTS: Patients who demonstrated by laparoscopy to have endometriosis showed a significantly increased incidence of tubal blockage during initial hysterosalpingography (HSG) (12/26, 46.1%) compared with controls (2/14, 14.3%). Patients with endometriosis also demonstrated significantly more frequently elevated tubal perfusion pressures (22/26; 84.6%) than women without disease (2/14, 14.3%) and significantly higher mean tubal perfusion pressures than women with normal pelvises (576 +/- 264 versus 450 +/- 268 mm Hg). CONCLUSION: Tubal blockage during initial HSG and elevated tubal perfusion pressures during selective salpingography are highly suggestive of tubal endometriosis. These data are the first evidence that tubal involvement with endometriosis may be more frequent than previously suspected. They also suggest that the performance of a gynecoradiological investigation, inclusive of selective salpingography, can greatly contribute to a presumptive diagnosis of endometriosis.

Gynaecoradiological uterine resection.

We assessed the feasibility of performing uterine surgery under fluoroscopic control in an ambulatory setting that does not require operating room time and general anaesthesia. Four uterine septae were resected and two cases of Asherman's syndrome were treated using fluoroscopically guided scissors. All six surgical procedures were successfully completed. Gynaecoradiological uterine resection (GUR) procedures, utilizing fluoroscopy guided scissors, are promising new techniques, which may allow the successful performance of uterine surgery in a cost effective ambulatory setting with no requirement of general anaesthesia.

The bubble test: a new tool to improve the diagnosis of endometriosis.

The objective of this study was to determine the clinical sensitivity and specificity of a bubbling phenomenon, including peritoneal surfaces, as a diagnostic test for endometriosis during laparoscopy. A prospectively controlled study of women with infertility of at least 1 year duration, who underwent laparoscopy, was conducted at a medical school-affiliated private infertility centre and research foundation. The study included 48 prospectively enrolled female infertility patients who underwent laparoscopy. Of these, 32 were found to suffer from endometriosis (group A) and 16 control patients did not show any evidence of disease (group B). The study involved the irrigation of the posterior cul-de-sac with short bursts of either saline or lactated Ringer's solution, utilizing a standard laparoscopic aspiration/irrigation system, and the subsequent observation for an excessive soap-like bubbling phenomenon (positive bubble test) in association with endometriosis. All 32 endometriosis patients (group A) demonstrated a positive bubble test. In contrast, only two of the 16 control patients (group B) were positive (P = 0.00242, Fisher's exact test; odds ratio, 8.000). A positive bubble test during laparoscopy was thus 100% sensitive and 88% specific for the diagnosis of endometriosis by laparoscopy, resulting in positive and negative predictive values of 94 and 100% respectively. Since the literature provides considerable evidence that the diagnosis of endometriosis during laparoscopy is frequently missed, a positive bubble test during laparoscopy therefore may be considered a reason to search further (possibly with biopsies) for endometriosis in the absence of obviously visible disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Target antigen(s) in endometrial autoimmunity of endometriosis.

OBJECTIVE: To obtain the molecular weights (MW) of endometrial antigens eliciting immunoglobulin (Ig) G auto-antibodies in all endometriosis patients irrespective of their place of origin or race, and to verify their specificity and immunogenicity. STUDY DESIGN AND RESULTS: We tested the serum and peritoneal fluid (P.F.) of 76 endometriosis patients and 24 controls from 4 cities against endometrial and implant antigens by Western blot analysis. Endometrial and implant antigens with MW of 34, 46/48, 64, 84, 94 and 120 kDa bound with IgG in serum and PF of most patients, but not the controls. Antigen(s) with MW of 64 kDa was reactive against serum or P.F. IgG of patients from all cities. Specificity: Endometrial and implant extracts did not react with monoclonal antibodies to WBC subsets and 5 sera with nuclear antibodies. Also, the presence of nuclear and endometrial antibodies did not correlate in 20 other patients with endometriosis. Immunogenicity: We immunized rabbits with the native and eluted (MW 29 to 68 kDa and > or = 68 kDa) endometrial and implant proteins. The antiserum had specific IgG binding to the same glandular epithelial antigens as those bound by the patient's serum. CONCLUSIONS: Endometrial antigens with MW of 34, 46/48, 64, 94 and 120 kDa, especially 64 kDa appear to be specific, immunogenic and relevant to endometrial autoimmunity in all patients with endometriosis.

Laparoscopic removal of twin cornual pregnancy after in vitro fertilization.

The laparoscopic management of tubal pregnancies by salpingostomy has become a clinical standard of care (5). Those surgeries usually are performed for tubal pregnancies that are located distally to the cornua and the intramural piece of the tube. We previously reported on the conservative surgical management of interstitial pregnancies (3). To our knowledge, cornual pregnancies have never before been approached laparoscopically. Such a surgical approach is reported here, involving a twin gestation in the left uterine cornua conceived by IVF in a women with bilaterally absent tubes.

Sonographic transcervical balloon tuboplasty.

The purpose of this study was to evaluate sonographic guidance for transcervical tubal catheterization and transcervical balloon tuboplasty of patients with bilateral proximal tubal occlusion. Cornual catheterization and transcervical balloon tuboplasty were performed under sonographic guidance. Injection of micro-bubble emulsion confirmed tubal recanalization. Tubal patency demonstrated by sonography was confirmed by injection of contrast material under fluoroscopy. Four women with bilateral proximal tubal occlusion confirmed by previous hysterosalpingogram and laparoscopy underwent sonographically guided transcervical balloon tuboplasty. Patients with distal or peritubal damage were excluded from this study. Bilateral tubal patency confirmed by sonography and subsequent fluoroscopy was achieved in all four patients. One patient conceived spontaneously, a month following the procedure, and delivered at term. Sonographically guided transcervical balloon tuboplasty can be performed successfully on patients with proximal tubal occlusion. Identification of the catheter tip and successful cannulation of the internal tubal ostia were easier to perform under fluoroscopy. Further improvements in sonographic equipment and catheter technology will hopefully eliminate radiation and replace fluoroscopy during the performance of transcervical balloon tuboplasty. Sonographic transcervical tubal catheterization may, therefore, become a simple and cost-effective procedure for the diagnosis and treatment of patients with proximal tubal occlusion.

Hysterosalpingography and selective salpingography in the differential diagnosis of chemical intrauterine versus tubal pregnancy.

OBJECTIVE: To determine the validity of hystersalpingography (HSG) and/or bilateral selective salpingography in the differential diagnosis of early (biochemical) intrauterine versus intratubal abortions. DESIGN: The study design involved the performance of HSG and selective salpingography in sequential patients with low declining beta-human chorionic gonadotropin (beta-hCG) values. SETTING: Medical School-affiliated Infertility Center. PARTICIPANTS: Four sequential pregnant infertility patients who demonstrated declining beta-hCG levels before pregnancy could be confirmed by ultrasound (chemical pregnancies). RESULTS: Three of four patients demonstrated a characteristic tubal opacification pattern in conjunction with a normally appearing endometrial cavity, considered diagnostic of an early tubal pregnancy. In contrast, a missed intrauterine pregnancy (IUP) demonstrated a characteristically abnormal endometrial cavity. CONCLUSIONS: Some early (chemical) pregnancy losses are intratubal rather than intrauterine. The correct differential diagnosis of early missed IUPs versus intratubal pregnancies is important because of its prognostic significance.

Breast disease programs in obstetrics and gynecology: a plea for training in mammography.

Obstetrics and gynecology residency programs have started to integrate structured breast disease teaching programs into the curricula. I suggest that mammography training should be the cornerstone of programs on the diagnosis of breast diseases. The implementation of such a program into a teaching department is described in an attempt to facilitate similar efforts elsewhere.

Ovarian development of the female child and adolescent: I. Morphology.

Ovarian morphology of 180 randomly selected females, aged 8-21, was investigated, utilizing standard sector scanning ultrasound techniques, at -1 year (1 year before menarche), year 0 (menarche) and years +1 to +8 (1-8 years postmenarche). According to strict morphologic criteria, seven ovarian patterns were recognized which varied in dominance with age in reference to menarche. Prior to menarche a multifollicular ovarian pattern (Type 1) dominates which after menarche is substituted by a predominantly active ovarian pattern (Type 5). Approximately 20% of postmenarcheal females do not develop this active pattern. In a relatively persistent percentage of females a microcystic (Type 2) ovarian pattern was recognized throughout all postmenarcheal years, suggestive of a normal transitional pattern from Type 1 to Type 5 ovaries. In contrast, multicystic (Type 3), hyperthecosis (Type 4), polycystic ("Mickey Mouse") (Type 6) and silent (Type 7) ovaries appear to represent abnormal ovarian developments. Based on percentage distributions, it is tempting to speculate that multicystic (Type 3) and/or hyperthecosis (Type 4) ovaries represent precursor ovaries to Type 6 (polycystic) ovaries. Confirmation of this hypothesis would have major clinical importance for the early diagnosis of the polycystic ovarian syndrome.