Elevated serum silicon levels in women with silicone gel breast implants

The metatolic fate of silicone gel leaked from an intact or ruptured prosthesis is unknown. In this study, serum was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon in 72 women with silicone gel breast implants and 55 control women (mean age 48 yr, both groups). Blood was drawn and processed using silicon-free materials. The mean silicon level in controls was 0.13±0.07 mg/L (range 0.06–0.35 mg/L), whereas in implant patients, the mean was significantly higher at 0.28±0.22 mg/L (range 0.06–0.87 mg/L) (P<0.01, Student'st-test with correction for unequal variances). Using the mean of the control group +2 SD as a cutoff for normal range (0.27 mg/L), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw, or the number of years with implants and silicon levels. The results suggest that serum silicon levels are elevated in many women with silicone gel breast implants. The chemical species involved and kinetics of this elevation remain to be determined.     

Variability in the properties of silicone gel breast implants.

Several generations of silicone gel breast implants have been produced by implant manufacturers. The primary material usually viewed as the base material in the manufacture of implants is polydimethylsiloxane. Polymeric reactions are notorious for their variability and nonuniformity. The elastomer used in different types of implants can have vastly different properties. Furthermore, the material properties associated with a particular type of implant can vary considerably from one lot to the next. Considering the various designs, styles, and manufacturing techniques associated with silicone gel implants, knowledge of the original properties of the implants before implantation is important in determining the effects of aging in vivo. This study was conducted to investigate differences in key mechanical and chemical properties of silicone gel breast implant materials. The two types of implants chosen for analysis were Silastic I and Silastic II control implants. Material property data were determined for both types of controls and significant differences were found in their values. Lot-to-lot variability was also investigated and found to be significant.     

Decision and management algorithms to address patient and food and drug administration concerns regarding breast augmentation and implants

During the U.S. Food and Drug Administration's advisory panel hearings to evaluate the premarket approval for conventional silicone gel implants on October 14 and 15, 2003, panel members and patient advocate representatives focused on four specific areas of concern: reoperation rates in primary breast augmentation; levels, depth, and methods of patient education and informed consent; modes, frequency, and management of silicone gel implant device failures, including management of "silent" ruptures; and methods of monitoring and managing symptoms or symptom complexes that may or may not be associated with connective tissue disease or other undefined symptom complexes. These concerns, with a reported 20 percent reoperation rate for primary augmentation within just 3 years, and a lack of concise, definitive management protocols addressing these areas of concern may have contributed to the Food and Drug Administration's rejection of the premarket approval, despite the panel's recommendation for approval. This article presents decision and management algorithms that have been used successfully for 7 years in a busy breast augmentation practice (Tebbetts and Tebbetts). The algorithms have been further expanded and refined by a group of surgeons with diverse experiences and expertise to address the following clinical situations that coincide with concerns expressed by patients and the Food and Drug Administration: implant size exchange, grade III to IV capsular contracture, infection, stretch deformities (implant bottoming or displacement), silent rupture of gel implants, and undefined symptom complexes (connective tissue disease or other). In one practice (Tebbetts and Tebbetts) that uses the TEPID system (tissue characteristics of the envelope, parenchyma, and implant and the dimensions and fill distribution dynamics of the implant), implant selection is based on quantified patient tissue characteristics, pocket selection is based on quantified soft-tissue coverage, and anatomic saline implants have fill volumes that are designed to minimize shell collapse and fold fatigue; in this practice, the algorithms contributed to a 3 percent overall reoperation rate in 1662 reported cases with up to 7 years of follow-up, compared with a 20 percent reoperation rate at 3 years in the 2003 premarket approval study.     

Biodurability of retrieved silicone gel breast implants

This study analyzed the shells of single-lumen silicone gel breast implants within the general context of device durability in vivo. The investigation included the major types of gel-filled implants that were manufactured in the United States in a 30-year period. The implants analyzed were Cronin seamed (two explants and one control), Silastic 0 and Silastic I (18 explants and seven controls), and Silastic II (22 explants and 43 controls). The biodurability of the explants was investigated with measurements of the mechanical and chemical properties of the various types of silicone gel control and explanted shells, with implantation times ranging from 3 months to 32 years. The shell properties measured for the controls and explants included the stress-strain relationships, tensile strength, elongation, tear resistance, moduli, cross-link density, and amount of extractable material in the shell. In addition, the mechanical properties of shells that had been extracted with hexane were analyzed for both explants and control implants. The silicone gel explants investigated in this study included some of the oldest explants of the various major types that have been tested to date. For assessment of long-term implantation effects, the data obtained in this study were combined with all known data from other institutions on the various major types of gel implants. The study also addressed the failure mechanisms associated with silicone gel breast implants. The results of the study demonstrated that silicone gel implants have remained intact for 32 years in vivo and that degradation of the shell mechanical and chemical properties is not a primary mechanism for silicone gel breast implant failure.     

The deposition of talc in patients with silicone gel-filled breast implants.

This study was initiated to understand why talc was found in the entrance wounds and pericapsular scars of patients with silicone breast implants. Twenty-five surgical gloves made between 1977 and 1992 by a major glove manufacturer were evaluated with infrared spectroscopy. Seven gloves manufactured before early 1983 contained talc. Later manufactured gloves contained calcium carbonate instead of talc. Talc-containing gloves were submitted to independent laboratories for scanning electron microscopic examination and x-ray microanalysis to obtain finer detail. Remnants of the mold-release agent talc were found in the matrix of the patient-contact side of the glove. Wetting studies showed that silicone oil (gel bleed) immediately wet the surface of rubber glove. After donning, silicone oil was massaged between the thumb and index finger of each washed, talc-containing glove for 1 minute and then daubed from the glove to a microscopic slide. The slide was viewed with polarized light microscopy for the presence of talc crystals. Transfer of talc occurred using silicone oil, but not saline, in each talc-containing glove. Three factors were likely involved in the greater talc deposition that occurred with patients undergoing silicone gel-filled breast implantation than in patients undergoing other surgical procedures. (1) The wetting of the gloves with silicone gel bleed from implants loosened the talc in the glove matrix. (2) Hand-intensive surgical use freed the talc from the gloves. (3) Loose talc adhered to the silicone elastomer of the breast implants and was deposited with implant placement.     

Textured-surface saline-filled silicone breast implants for augmentation mammaplasty

The earliest silicone breast implants were smooth-surface, silicone rubber devices filled with either silicone gel or saline. Because of persistent problems with capsular contracture, polyurethane-covered silicone implants were developed as an alternative. Particularly in the short run, these alternatives proved highly successful at reducing the incidence of capsular contracture. By 1990, polyurethane-covered implants were rapidly becoming the preferred implant choice of many plastic surgeons, but for legal, regulatory, financial, and safety reasons they were withdrawn from the market by Bristol-Myers in 1991. Meanwhile, during the late 1980s, surface texturing and improved materials became available on other silicone breast implants and expanders. Most studies suggest that textured-surface silicone gel-filled implants, saline-filled implants, and tissue expanders have less frequent capsular contracture than their smooth-surface counterparts.     

Silicone gel-filled breast implant integrity: a retrospective review of 478 consecutively explanted implants

Concern has been expressed over the long-term integrity of silicone gel breast implants. There are no large series representing experience with these implants outside of the United States. A retrospective case note review of explanted silicone breast implants was performed; 478 implants have been explanted during the past 11 years and relate to the use of these devices since 1971. Loss of implant integrity was not simply related to its age in vivo. Failure was more likely with implants of the late 1970s and early 1980s (second generation) and with subpectoral placement. Implant failure was independent of capsular contracture as the indication for removal (p = 0.09). There is no evidence that the currently used textured silicone gel breast implants are subject to the same loss of integrity as previous examples of these devices. The life span of these implants, the first of which are approaching 10 years in vivo, is at present unknown. Information concerning the integrity of silicone gel breast implants is essential in the current climate for counseling of both new and old implant recipients.     

The effect of breast implants on the radiographic detection of microcalcification and soft-tissue masses

Current implants for breast augmentation containing silicone gel, saline, or both can totally obscure mammographic detection of microcalcifications and soft-tissue masses. To investigate the possibility of developing a more radiolucent implant, radiographs were obtained of silicone shells that contained silicone gel, saline, silicone gel and saline, polyurethane-covered silicone gel, gelatin, sunflower oil, and peanut oil. All radiographs were obtained using a Siemens Mammomat by placing the implant over an American College of Radiology mammography phantom. Results were measured by the ability to visualize or resolve the artifacts in the mammography phantom. The silicone shell alone minimally altered artifact resolution. Silicone shells filled with silicone gel, silicone gel and saline, saline alone, polyurethane-covered silicone gel, and gelatin were equal in radiodensity and completely obscured all phantom artifacts. Silicone shells filled with peanut oil and sunflower oil had equal radiodensity and allowed visualization of large microcalcifications and some soft-tissue masses. Current implants used for augmentation mammaplasty can totally obscure mammographic detection of microcalcifications and soft-tissue masses. A more radiolucent breast implant is possible, and further research is needed to define the best filler material and test its biocompatibility.     

Biocompatibility of radiolucent breast implants

Current implants for breast augmentation containing silicone gel, saline, or both are radiopaque on mammographic examination and can totally obscure microcalcifications and soft-tissue masses. The effect of these implants on the detection of early breast cancers in patients who have undergone augmentation mammaplasty remains unproven and controversial. Implants filled with medium-chain triglycerides (peanut oil) are radiolucent on mammographic examination and allow visualization of both soft-tissue masses and microcalcifications. To investigate the biocompatibility of radiolucent implants, 10 cc of sterile, nonpyrogenic peanut oil was injected subcutaneously into rats using silicone gel as a control. Twenty-one rabbits had two 125-cc silicone shell implants inserted on either side of the chest wall. The right-sided shell was filled with 125 cc of sterile saline, and the left-sided shell was filled with 125 cc of sterile, nonpyrogenic peanut oil. Results were determined by both histologic and radiographic examination. Rats injected with peanut oil equivalent to 7 percent of their body weight rapidly absorbed the freely injected oil without detriment. Histologic examination of the lungs, liver, kidneys, and tissues adjacent to the injection sites demonstrated no abnormalities. There was no evidence of allergic, toxic, inflammatory, or neoplastic response. Eighteen of 21 rabbits survived more than 3 months. Radiographs showed the oil-filled implants to be radiolucent, whereas the saline-filled controls obscured the surrounding soft and bony tissues. Histologic examination demonstrated a fibrous capsule surrounding both types of implants. Histologic examination of the lungs, liver, and kidneys showed no significant abnormalities. These and previous studies have shown peanut oil to be biocompatible when freely injected either intramuscularly or subcutaneously. This study demonstrates that a radiolucent, peanut oil-filled implant is biocompatible in animals and that further long-term studies for its use in humans are merited.     

Analysis of the soft-tissue response to components used in the manufacture of breast implants: rat animal model.

The implant-tissue response to the silicone gel mammary prosthesis requires a more thorough evaluation in light of recent concerns related to human connective-tissue diseases, contracture, infection, and neoplasia. The silicone prosthesis is not a homogeneous implant but is a milieu of various silicone chemistries. Silicone polymer precursors and prosthesis components (silicone shells, shells extracted of their low-molecular-weight components, silica-free silicone, silicone oil, fumed silica, and silicone extract) were implanted subcutaneously using a nonhemorrhagic technique into the backs of Lew/SsN rats (n = 90), two implants per rat, for periods of 7, 14, 28, 56, and 90 days for a total of 6 implants per material per time period. Histologic analysis was performed on specimens from the harvested soft tissue. The intensity of the cellular and capsular response was lowest for the silicone oil and increased as the material's molecular weight increased and material compliance decreased. Fumed silica elicited the most highly reactive cellular response. From this study it is apparent that the polymer's molecular weight influences its migration, encapsulation, and intensity of cellular response. Further, the silicone extract distillate elicited a highly intense cellular response with pronounced lymphocyte invasion. The human relevance of this work awaits further correlation with implant retrieval and in vivo performance.     

"Bleeding" of silicone from bag-gel breast implants, and its clinical relation to fibrous capsule reaction.

We present evidence of the following. 1. Modern silicone bag-gel breast implants leak silicone gel through the bag. 2. The amount of silicone leaked by an intact implant varies from one implant to another, and is not constant for any type or brand. 3. The leaked silicone, together with fibrous thickening and various degrees of inflammation will be found in capsules surrounding the implants if extensive biopsies are taken and many sections are examined.     

Radiolucent prosthetic gel.

The successful use of silicone breast implants is complicated by their interference with mammography. We have evaluated clinically available implant filling materials and found that a new Bio-Oncotic gel approximates the radiolucency of normal breast tissue. Silicone implants completely obscure areas of the breast in mammography. Recently proposed as a filler material, peanut oil is significantly more radiolucent than normal tissue. Physiologic saline solution compares favorably as a tissue-density-simulating substance. However, saline's lack of lubricating properties results in leakage, making it less than optimal. Bio-Oncotic gel is biologically compatible. We conclude that this gel is the most appropriate filler for breast prostheses. Clinical studies are indicated.     

The correction of capsular contracture by conversion to "dual-plane" positioning: technique and outcomes

Little has been published regarding the treatment of patients with long-established capsular contracture after previous submuscular or subglandular breast augmentation. This study reviews 7 years of experience in treating established capsular contracture after augmentation mammaplasty by relocating implants to the "dual-plane" or partly subpectoral position. A retrospective chart review was performed on all patients who were treated for capsular contracture using this technique between 1993 and 1999. Data collected included the date of the original augmentation, the original implant location, date of revision and type of implant used, length of follow-up, outcome, and any ensuing complications. Different surgical techniques were used, depending on whether the prior implant was located in a subglandular or submuscular plane. All patients had revisions such that their implants were relocated to a dual plane, with the superior two thirds or so of the implant located beneath the pectoralis major muscle and the inferior one third located subglandularly. Of 85 patients reviewed, 54 had their original implants in a submuscular position and 31 had their initial augmentation in a subglandular position. Of the 54 patients whose implants were initially submuscular, 23 patients (43 percent) had silicone gel implants, 15 patients (28 percent) had double-lumen implants, and the remaining 16 patients (30 percent) had saline implants. Of the 31 patients whose implants were initially subglandular, 20 patients (65 percent) had silicone gel implants, three patients (10 percent) had double-lumen implants, and the remaining eight patients (26 percent) had saline implants. Fifty-one patients (60 percent) had replacement with saline implants (37 smooth saline, 14 textured saline), whereas 34 (40 percent) had silicone gel implants (seven smooth gel, 27 textured gel). The average time from previous augmentation to revision was 9 years 9 months. The average follow-up time after conversion to the dual-plane position was 11.5 months. Only three of 85 patients required reoperation for complications, all of which involved some degree of implant malposition. Of patients converted to the dual plane, 98 percent were free of capsular contracture and were Baker class I at follow-up, whereas 2 percent were judged as Baker class II. There were no Baker level III or IV contractures at follow-up. The dual-plane method of breast augmentation has proved to be an effective technique for correcting established capsular contracture after previous augmentation mammaplasty. This technique appears to be effective when performed with either silicone or saline-filled implants.     

Biomechanical validation of finite element models for two silicone metacarpophalangeal joint implants

Silicone implants are used for prosthetic arthroplasty of metacarpophalangeal (MCP) joints severely damaged by rheumatoid arthritis. Different silicone elastomer MCP implant designs have been developed, including the Swanson and the NeuFlex implants. The goal of this study was to compare the in vitro mechanical behavior of Swanson and NeuFlex MCP joint implants. Three-dimensional (3D) finite element (FE) models of the silicone implants were modeled using the commercial software ANSYS and subjected to angular displacement from 0 deg to 90 deg. FE models were validated using mechanical tests of implants incrementally bent from 0 deg to 90 deg in a joint simulator. Swanson size 2 and 4 implants were compared with NeuFlex size 10 and 30 implants, respectively. Good agreement was observed throughout the range of motion for the flexion bending moment derived from 3D FE models and mechanical tests. From 30 deg to 90 deg, the Swanson 2 demonstrated a greater resistance to deformation than the NeuFlex 10 and required a greater bending moment for joint flexion. For larger implant sizes, the NeuFlex 30 had a steeper moment-displacement curve, but required a lower moment than the Swanson 4, due to implant preflexion. On average, the stress generated at the implant hinge from 30 deg to 90 deg was lower in the NeuFlex than in the Swanson. On average, starting from the neutral position of 30 deg for the preflexed NeuFlex implant, higher moments were required to extend the NeuFlex implants to 0 deg compared with the Swanson implants, which returned spontaneously to resting position. Implant toggling within the medullary canals was less in the NeuFlex than in the Swanson. The differential performance of these implants may be useful in implant selection based on the preoperative condition(s) of the joint and specific patient functional needs.     

Skeletal effects of oral oestrogen compared with subcutaneous oestrogen and testosterone in postmenopausal women.

STUDY OBJECTIVE--To compare oral and implanted oestrogens for their effects in preventing postmenopausal osteoporosis. DESIGN--Non-randomised cohort study of postmenopausal women treated with oral or depot oestrogens and postmenopausal controls. SETTING--Gynaecological endocrine clinic in tertiary referral centre. PATIENTS--Oral treatment group of 37 postmenopausal women (mean age 57.5 years, median 8.75 years from last menstrual period), compared with 41 women given oestrogen implants (mean age 56.2 years, median 9.5 years from last menstrual period) and 36 controls (mean age 51.8 years, median 2.0 years from last menstrual period). Weight was not significantly different among the groups. INTERVENTIONS--Oral treatment group was given continuous treatment with cyclic oestrogen and progesterone preparations (Prempak C or Cycloprogynova) for a median of 8.0 years. Implant group was given subcutaneous implants of oestradiol 50 mg combined with testosterone 100 mg, on average six monthly for a median of 8.5 years. Controls were not treated. END POINT--Significant increase in bone density. MEASUREMENTS AND MAIN RESULTS--Bone density measured by dual beam photon absorptiometry was 1.02 (SD 0.13) g hydroxyapatite/cm2 in implant group versus 0.89 (0.11) in oral group (p less than 0.01) and 0.87 (0.14) in controls (p less than 0.01). Serum oestradiol concentration in implant group was (median) 725 pmol/l versus 170 pmol/l in oral group (p less than 0.01) and 99 pmol/l in controls (p less than 0.01). Serum follicular stimulating hormone was median 1 IU/l (range 1-11) in implant group (equivalent to premenopausal values) versus 43 (4-94) IU/l in oral group (p less than 0.01) and 72 (28-99) IU/l in controls (p less than 0.01). CONCLUSIONS--Subcutaneous oestrogen is more effective than oral oestrogen in preventing osteoporosis, probably owing to the more physiological (premenopausal) serum oestradiol concentrations achieved. It also avoids problems of compliance that occur with oral treatment.     

"Out points" criteria for breast implant removal without replacement and criteria to minimize reoperations following breast augmentation

Breast augmentation is a totally elective, medically unnecessary procedure, and surgeons and patients must prioritize minimizing tradeoffs, costs, and risks at the primary operation and at reoperations. At the U.S. Food and Drug Administration's advisory panel hearings in October of 2003 to consider approval of conventional silicone gel implants, data documented an overall reoperation rate of 20 percent at just 3 years after primary breast augmentation. Subsequently, the premarket approval was not granted. Similarly high reoperation rates have been reported in previous saline and silicone gel premarket approval studies over the past two decades, demonstrating that high reoperation rates are not device dependent and suggesting a need to reexamine surgical management criteria. Bilateral implant removal without replacement limits additional reoperations in a wide range of clinical situations. Surgeons and patients often prefer other options to avoid removal without replacement, but other options carry a higher tradeoffs, costs, and risks to the patient. If minimizing tradeoffs, costs, and risks of reoperations is a priority, surgeons must define and patients must understand and accept "out points," that is, specific criteria for bilateral implant removal without replacement. Defining out points is challenging. Enforcing them when difficult clinical situations occur is even more challenging. This article presents out points that have been incorporated into staged, repetitive informed consent documents and used in the author's practice for more than 10 years. In peer-reviewed and published reports of more than 1600 patients, these out points criteria, in conjunction with the TEPID system (tissue characteristics of the envelope, parenchyma, and implant and the dimensions and fill distribution dynamics of the implant) of implant and pocket selection based on individual patient quantifiable tissue criteria and surgical techniques that minimize tissue trauma and bleeding, resulted in an overall reoperation rate of 3 percent in 1662 reported cases with up to 7 years of follow-up, compared with the 20 percent reoperation rate at 3 years in the most recent Food and Drug Administration study.     

Synchronization of estrus and fertility in goats with norgestomet ear implants

Estrus was synchronized in 64 dairy goats in July with norgestomet ear implants. Half the does received ear implants that contained 6 mg norgestomet and the remaining does received implants that contained 3 mg. Implants were left in place for 11 days. Each doe received i.m. injections of 400 IU PMSG and 50 mug cloprostenol 24 hours prior to implant removal. Twenty-eight of 32 does (87.5%) that received 6 mg or 3 mg norgestomet exhibited onset of estrus within 24 hours of implant removal. All does had exhibited onset of standing estrus by 43 hours after implant removal. Does were hand-mated to fertile bucks twice daily while in standing estrus. There were no differences between does implanted with 6 mg or 3 mg in fertility to the induced estrus (74.2% vs 75% kidding), mean length of gestation (151.0 +/- 3.2 vs 151.6 +/- 2.0 days), mean number of kids per doe (2.1 +/- 0.8 vs 2.3 +/- 0.7) or in mean kid weights (3.10 +/- 0.80 vs 3.06 +/- 0.86 kg) (6 mg vs 3 mg, respectively). It was concluded that ear implants that contained 3 mg of norgestomet were equally as effective as implants that contained 6 mg for synchronization of estrus in dairy goats.     

Self-reported diseases and symptoms by rupture status among unselected Danish women with cosmetic silicone breast implants

Epidemiologic evidence does not support an association between silicone breast implants and connective tissue or other rheumatic diseases. However, a recent study has suggested that women with ruptured implants may be at increased risk of developing fibromyalgia. An analysis of adverse health outcomes according to breast implant rupture status was conducted in 238 unselected Danish women with cosmetic silicone breast implants. Ninety-two of the women had definite implant rupture, and 146 had intact implants as determined by magnetic resonance imaging. Before undergoing imaging, the women provided blood samples and completed a self-administered questionnaire. Women with ruptured implants overall, and the subgroup with extracapsular ruptures (n = 23), were compared with women with intact implants regarding a number of self-reported diseases and symptoms and the presence of specific autoantibodies, such as antinuclear antibodies, rheumatoid factor, and cardiolipin immunoglobulin G and M antibodies. Overall, there were no differences in the occurrence of self-reported diseases or symptoms or in the presence of autoantibodies between women with intact implants and women with ruptured implants, including extracapsular rupture. The only exception was capsular contracture, which was reported six times more frequently by women with extracapsular ruptures than by women with intact implants (OR, 6.3; 95 percent CI, 1.7 to 23.5). In conclusion, this study of unselected women with silicone breast implants could establish no association between silicone implant rupture and specific diseases or symptoms related to connective tissue disease or other rheumatic conditions, except for an excess of capsular contracture among women with extracapsular rupture.     

Metal accumulation,filtration and O(2) uptake rates in the mussel Perna perna (Mollusca: Bivalvia) exposed to Hg(2+), Cu(2+) and Zn(2+)

Tissue metal concentrations, filtration and oxygen uptake rates were investigated for Perna perna (Bivalvia: Mollusca) during exposure to Hg(2+), Cu(2+) and Zn(2+) (50 microg/l for 24 days, and 24 days recovery with no metal). Hg and Cu tissue levels increased with exposure time, reaching maximum levels after 24 days (87.5 microg Hg/g dry mass and 45 microg Cu/g dry mass, respectively). Zn levels peaked after 4 days exposure (to 233 microg Zn/g dry mass) and stabilized thereafter. Accumulated metal was rapidly lost from tissues when mussels were returned to uncontaminated seawater, suggesting that tissue concentration data may be of limited use in biomonitoring situations where environmental metals fluctuate to low levels. Filtration rates fell below control rates during Hg(2+) exposure, and became elevated again during the recovery period. Cu(2+) and Zn(2+) exposure had little effect on filtration, but suppressed oxygen uptake. During recovery, oxygen uptake of Cu(2+) and Zn(2+) exposed mussels was elevated above the controls. Filtration and oxygen uptake rates were not correlated, but rather responded in different ways to metal pollution. While these physiological responses of P. perna may be of limited use in biomonitoring, they could indicate how populations may respond to marine pollution.     

Suppression of follicle wave emergence in cyclic ewes by supraphysiologic concentrations of estradiol-17beta and induction with a physiologic dose of exogenous ovine follicle-stimulating hormone

Follicle waves are preceded by follicle-stimulating hormone (FSH) peaks in ewes. The purpose of the present study was to see whether estradiol implant treatment would block FSH peaks to create a model in which the effect of the timing and mode of FSH peaks could be studied by ovine FSH (oFSH) injection. In Experiment 1, 10 ewes received estradiol-17beta implants on Day 4 after ovulation (Day 0, day of ovulation); five ewes received large implants, and five ewes received small implants. Five control ewes received empty implants. In Experiment 2, 12 ewes received large implants on Day 4. On Day 9, six ewes received oFSH twice, 8 h apart (0.5 microg/kg; s.c.). Implants were left in place for 10 days in both experiments. In both studies, ovarian ultrasonography and blood sampling was done daily. In Experiment 1, estradiol concentrations were significantly higher in ewes with large implants (10.4 +/- 0.7 pg/ml) compared with controls (3.9 +/- 0.7 pg/ml) and ewes with small implants (5.4 +/- 0.7 pg/ml; P < 0.001). A significant reduction was found in mean FSH peak concentration (31%; P < 0.05) and FSH peak amplitude (45%; P < 0.05) in ewes with large implants compared with controls. Mean and basal FSH concentrations were unaffected by the large implants. The large implants halted follicle-wave emergence between Day 0 and 8 after implant insertion. The small follicle pool (2-3 mm in diameter) was unaffected by the large implants. When oFSH was injected into ewes with large implants, a follicle wave emerged 1.5 +/- 0.5 days after injection; however, in ewes given saline alone, a follicle wave emerged 4.8 +/- 0.8 days after injection (P < 0.01). We concluded that truncation of FSH peaks by estradiol implants prevented follicle-wave emergence, but injection of physiologic concentrations of oFSH reinitiated follicle-wave emergence.